LMNA and Hutchinson-Gilford Progeria Syndrome: Association Evidence

At a glance

Association overview

Clinical actionability

Approved therapy Lonafarnib

Genetic testing Available (GTR)

Clinical trials6 targeting this disorder / 36 total

Inheritance Autosomal dominant, Autosomal recessive

Onset Infancy, Neonatal

ClinVar records 256 variants in LMNA linked to this disorder, 37 of them classified pathogenic or likely pathogenic.^[2] 154 clinical features are documented for the disorder.^[1][3][6] Clinically, it is a rare disorder (prevalence <1/1000000), and onset is typically reported in infancy, neonatal.^[7]

At the molecular level, LMNA and Hutchinson-Gilford Progeria Syndrome converge on 4 shared biological pathways, including Lamin A processing pathway and Influence of laminopathies on Wnt signaling.^{[8][9][10][11]} LMNA is targeted by Lonafarnib, a compound approved for clinical use. Of 36 clinical trials reached through LMNA compounds, 6 target Hutchinson-Gilford Progeria Syndrome directly; the rest study those compounds in other indications.^[12][7] 64 publications jointly reference LMNA and Hutchinson-Gilford Progeria Syndrome.^[13][14][15]

Evidence strength

4 curated sources1 genetic test source

Gene category Protein Coding

Disorder categories Bone diseases, Skin diseases

Provenance

Evidence and sources

OMIM®Curated150330

Molecular basis known

ClinVarCuratedhutchinson-gilford syndrome

Pathogenic, Likely pathogenic

OrphanetCuratedORPHA16364

Causative germline mutation

UniProtKB/Swiss-ProtCuratedhutchinson_gilford_progeria_syndrome

Causative variation

GTRGenetic testhutchinson_gilford_progeria_syndrome

Genetic Tests

Sourced from ^{[1][2][3][4][5]}

LMNA

The gene

AI-generated gene summary · distilled from the cited source summaries below

LMNA encodes lamin A/C, a pair of intermediate filament proteins that form the nuclear lamina and provide structural support to the nucleus. These isoforms link the nuclear envelope to chromatin, placing LMNA at the center of nuclear architecture. During mitosis, lamina organization is reversibly disassembled as lamin proteins are phosphorylated.

Beyond structural support, lamin A/C helps regulate nuclear integrity, chromatin organization, and DNA repair. It recruits XRCC4 and IFFO1 to double-strand breaks, connecting LMNA to DNA damage repair processes. The protein is localized to the nuclear envelope, nuclear lamina, nuclear matrix, and nuclear membrane, and its expression is high in brain, endocrine system, and respiratory system tissues.

Pathogenic variants in LMNA are reported in Hutchinson-Gilford progeria syndrome, Emery-Dreifuss muscular dystrophy 2, and dilated cardiomyopathy 1A. LMNA also has reported variant associations with familial partial lipodystrophy type 2 and hereditary motor and sensory neuropathy, Okinawa type. The gene is therefore clinically important in disorders affecting the musculoskeletal, cardiovascular, and metabolic systems.

Gene summaries 1 sources

1 Summary(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Source	Text
NCBI Gene	The protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]

Sourced from ^[16]

Hutchinson-Gilford Progeria Syndrome

The disorder

AI-generated disorder summary · distilled from the cited disorder sources

Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant premature aging disorder with onset usually within the first year of life. It is caused by mutation in LMNA on chromosome 1q22; the gene encodes lamin A, and mutation produces an abnormal lamin A protein called progerin. Some patients with heterozygous LMNA mutations have a similar phenotype with later onset in late childhood or early teenage years and longer survival than classic disease.

Clinical features include profound growth deficiency, failure to thrive, extreme short stature, low body weight, loss of subcutaneous fat, lipodystrophy, early alopecia, aged-looking or sclerotic skin, decreased joint mobility, progressive joint contractures, osteolysis, dental abnormalities, and characteristic facial features such as prominent or protruding eyes, a thin or narrow nose with a beaked tip, thin lips, small mouth or chin, micrognathia, and protruding ears. Motor and mental development are normal, and cognitive development is typically normal. Other reported features include high-pitched voice, nail dystrophy or nail hypoplasia, lagophthalmos, dry eye with risk of exposure keratitis, low-frequency conductive hearing loss, hip dislocations, coxa valga, and narrowed upper thorax.

Severe, progressive arteriosclerosis affects multiple body systems and leads to cardiovascular and cerebrovascular disease beginning in childhood. Cardiovascular compromise is life-threatening and is the major cause of early death. Without lonafarnib treatment, average age at death is about 14.5 years, with reported range 6-20 years; lonafarnib treatment extends average lifespan to approximately 18.7 years.

Disorder summaries 7 sources

7 Summary(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Source	Summary
Disease Ontology	A progeroid syndrome characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons that has material basis in mutation in the LMNA gene on chromosome 1q22.
MedlinePlus Genetics	Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not affect intellectual development or the development of motor skills such as sitting, standing, and walking. People with Hutchinson-Gilford progeria syndrome experience severe hardening of the arteries (arteriosclerosis) beginning in childhood. This condition greatly increases the chances of having a heart attack or stroke at a young age. These serious complications can worsen over time and are life-threatening for affected individuals.
UniProtKB/Swiss-Prot	Rare genetic disorder characterized by features reminiscent of marked premature aging.
OMIM®	Hutchinson-Gilford progeria syndrome is a rare disorder characterized by short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early death. Cognitive development is normal. Onset is usually within the first year of life (review by Hennekam, 2006). The designation Hutchinson-Gilford progeria syndrome appears to have been first used by DeBusk (1972). A subset of patients with heterozygous mutations in the LMNA gene and a phenotype similar to HGPS have shown onset of the disorder in late childhood or in the early teenage years, and have longer survival than observed in classic HGPS (Chen et al., 2003; Hegele, 2003). Other disorders with a less severe, but overlapping phenotype include mandibuloacral dysplasia (MADA; 248370), an autosomal disorder caused by homozygous or compound heterozygous mutations in the LMNA gene, dilated cardiomyopathy with hypergonadotropic hypogonadism (212112), caused by heterozygous mutation in the LMNA gene, and Werner syndrome (277700), an autosomal recessive progeroid syndrome caused by homozygous or compound heterozygous mutations in the RECQL2 gene (604611).
Orphanet	Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant and premature aging disease, beginning in childhood and characterized by growth reduction, failure to thrive, a typical facial appearance (prominent forehead, protuberant eyes, thin nose with a beaked tip, thin lips, micrognathia and protruding ears) and distinct dermatologic features (generalized alopecia, aged-looking skin, sclerotic and dimpled skin over the abdomen and extremities, prominent cutaneous vasculature, dyspigmentation, nail hypoplasia and loss of subcutaneous fat).
GARD	Hutchinson-Gilford progeria syndrome leads to extreme premature aging and affects many different body systems. The symptoms begin within a year of life with poor growth and weight gain. Children with Hutchinson-Gilford progeria syndrome have a characteristic facial appearance with a large head, small mouth and chin, narrow nose and large eyes. Other symptoms include baldness, loss of fat under the skin, and dental and joint abnormalities. They also often have symptoms typically seen in much older people including joint stiffness, hip dislocations and severe, progressive heart disease. Intelligence is typically normal. Hutchinson-Gilford progeria syndrome is caused by a genetic variant in the LMNA gene. This variant usually arises as a new change in the genetic material and is not inherited from a parent. Diagnosis is based on the symptoms, clinical exam, and may be confirmed by the results of genetic testing.
Wikipedia	Progeria (also Hutchinson-Gilford syndrome or Hutchinson-Gilford progeroid syndrome; HGPS) is a type of progeroid syndrome. A single gene mutation is responsible for causing progeria. The affected gene, known as lamin A (LMNA), makes a protein necessary for holding the cell nucleus together. When this gene mutates, an abnormal form of lamin A protein called progerin is produced. Progeroid syndromes are a group of diseases that cause individuals to age faster than usual. People born with progeria typically live until their mid- to late-teens or early twenties. Severe cardiovascular complications usually develop by puberty, later on resulting in death.

Prevalence

<1/1000000 (Point prevalence, Worldwide)<1/1000000 (Prevalence at birth, Worldwide)

All documented features 154 features

154 Symptom(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Symptom	Source
circumoral cyanosis	OMIM®
conductive hearing loss	OMIM®
coxa valga	Orphanet
craniofacial disproportion	HPO
lack of skin elasticity	HPO
myocardial infarction	HPO
narrow nasal ridge	Orphanet
persistence of primary teeth	HPO
skin mottling	OMIM®
absent eyebrow	Orphanet
aminoaciduria	OMIM®
ankyloglossia	HPO
dental crowding	OMIM®
elevated systolic blood pressure	OMIM®
female hypogonadism	HPO
osteoarthritis	HPO
premature skin wrinkling	HPO
shallow orbits	Orphanet
abnormal mitral valve morphology	HPO
aortic valve calcification	HPO
abnormal thorax morphology	HPO
delayed closure of fontanel	OMIM®
high palate	Orphanet
hypertension	Orphanet
hypoplastic male external genitalia	Orphanet
limited wrist movement	Orphanet
osteolysis	HPO
shuffling gait	HPO
generalized osteoporosis	HPO
impacted tooth	Orphanet
limitation of movement at ankles	HPO
cyanosis	HPO
farsightedness	OMIM®
generalized abnormality of skin	HPO
micrognathia	Orphanet
mitral valve calcification	HPO
nocturnal lagophthalmos	Orphanet
osteolytic defects of the distal phalanges of the hand	HPO
short lingual frenulum	Orphanet
short stature	OMIM®
stroke	Orphanet
avascular necrosis	Orphanet
carotid artery occlusion	Orphanet
midface retrusion	HPO
corneal dryness	OMIM®
exertional dyspnea	Orphanet
hypermelanotic macule	Orphanet
mitral regurgitation	Orphanet
insulin resistance	OMIM®
intracranial hemorrhage	Orphanet
limited hip movement	HPO
mitral stenosis	HPO
prominent umbilicus	Orphanet
premature coronary artery atherosclerosis	HPO
thin calvarium	OMIM®
short clavicles	Orphanet
sparse eyebrows	OMIM®
upper airway obstruction	Orphanet
absence of subcutaneous fat	Orphanet
corneal ulceration	HPO
hip pain	Orphanet
hypodontia	Orphanet
joint stiffness	HPO
left ventricular systolic dysfunction	HPO
limitation of joint mobility	HPO
normal birth weight	OMIM®
severe failure to thrive	Orphanet
transient ischemic attack	Orphanet
abnormal aortic valve morphology	Orphanet
abnormally high-pitched voice	Orphanet
alopecia totalis	Orphanet
convex nasal ridge	HPO
corneal opacity	HPO
delayed eruption of teeth	Orphanet
growth delay	HPO
patchy alopecia	Orphanet
precocious atherosclerosis	HPO
reduced bone mineral density	HPO
short chin	Orphanet
angina pectoris	HPO
decreased serum leptin	Orphanet
dystrophic toenail	Orphanet
elevated serum phosphorus	OMIM®
left ventricular diastolic dysfunction	Orphanet
loss of eyelashes	HPO
prolonged prothrombin time	OMIM®
prominent eyes	OMIM®
retrognathia	Orphanet
sclerodermatous skin changes	OMIM®
sparse eyelashes	OMIM®
alopecia	OMIM®
angina	OMIM®
dermal atrophy	Orphanet
dystrophic nails	OMIM®
ectopic calcification	HPO
genu valgum	OMIM®
prominent ear helix	HPO
skin dimpling	OMIM®
weight loss	HPO
broad nasal tip	OMIM®
conductive hearing impairment	HPO
delayed closure of anterior and posterior fontanel	OMIM®
hip dislocation	Orphanet
prominent cutaneous vasculature	OMIM®
pubertal developmental failure in females	Orphanet
elevated diastolic blood pressure	OMIM®
limited shoulder movement	Orphanet
raynaud phenomenon	Orphanet
relative macrocephaly	HPO
thin vermilion border	Orphanet
transient ischemic attacks (tias)	OMIM®
abnormality of the nasal tip	Orphanet
aortic regurgitation	Orphanet
atherosclerosis	Orphanet
high-frequency sensorineural hearing impairment	HPO
low-frequency sensorineural hearing impairment	HPO
muscular atrophy	OMIM®
ventricular hypertrophy	HPO
aortic valve stenosis	HPO
exposure keratitis	OMIM®
narrow mouth	Orphanet
papule	Orphanet
phalangeal contractures	OMIM®
premature atherosclerosis	OMIM®
progressive clavicular acroosteolysis	Orphanet
abnormal nasal tip morphology	HPO
delayed menarche	HPO
dystrophic fingernails	Orphanet
elevated platelet count	OMIM®
lipodystrophy	OMIM®
ovoid vertebrae	OMIM®
widened sutures	OMIM®
distal phalangeal tufting	OMIM®
osteopenia	OMIM®
short nails	OMIM®
failure to thrive	OMIM®
lateral clavicle resorption	OMIM®
narrow nasal tip	HPO
osteoporosis	OMIM®
acroosteolysis of distal phalanges	OMIM®
calcaneovalgus	OMIM®
delayed tooth eruption	OMIM®
malar flattening	HPO
ogival palate	OMIM®
pulmonary arterial hypertension	HPO
bitemporal bossing	OMIM®
narrow nasal bridge	OMIM®
prominent scalp veins	OMIM®
prominent superficial blood vessels	HPO
skin hyperpigmentation	OMIM®
congestive heart failure	HPO
flexion contractures	OMIM®
hypoplastic mandible	OMIM®
skin hypopigmentation	OMIM®

Additional disorder information

Aliases

HGPSProgeriaHutchinson Gilford SyndromeHutchinson-Gilford DiseaseHutchinson-Gilford SyndromeHutchinson-Gilford ProgeriaProgeria SyndromeProgeroid LaminopathiesProgeria Of ChildhoodHutchinson-Gilford-Progeria Syndrome

External resources

GeneReviews Expert-authored clinical summary for LMNA (NCBI Bookshelf)Genetic Testing Registry (GTR) Available genetic tests for this condition OMIM® Clinical synopsis and molecular genetics Orphanet Rare-disease summary and epidemiology Monarch Initiative Cross-species disease knowledge graph PubMed Latest literature on this gene and disorder

Database identifiers

Disease OntologyDOID:3911

ICD-10E34.8

ICD-111520135105

MedGenC0033300

MedGenC2750285

MedGenCN070028

MeSHD011371

MONDOMONDO:0008310

NCItC34951

OMIM®176670

OMIM® (phenotypic series)PS176670

OrphanetORPHA740

SNOMED CT190590004

UMLSC0033300

Sourced from ^[1][3][6]

Phenotype

Clinical features

ClinVar and variant evidence

Genetic basis

256 clinical variant(s)

Pathogenic

Pathogenic/Likely pathogenic

Likely pathogenic

Uncertain significance

168

Likely benign

Benign

Not provided

Variant spectrum by molecular consequence

Missense 168Intronic 74Synonymous 345′UTR 22Splice donor 4Frameshift 3Nonsense 33′UTR 2In-frame del 1Splice acceptor 1

Categories are non-exclusive: a variant with more than one molecular consequence is counted under each, so these counts can exceed the variant total. Variants with no reported consequence are omitted here.

Reported origin: Germline (244) · De novo (9) · Maternal (1). A variant may report more than one origin (counted under each); “Unknown / Not provided” is excluded.

Clinical variants 256 variants

256 Variant(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Rs Number	ClinVar ID	Name	Clinical Significance	Nucleotide Change	Protein Change
61672878	14495	NM_170707.4(LMNA):c.1130G>A (p.Arg377His)	Pathogenic	G/A	R265H
267607618	66800	NM_170707.4(LMNA):c.1294C>T (p.Gln432Ter)	Pathogenic	C/T
57920071	14489	NM_170707.4(LMNA):c.1444C>T (p.Arg482Trp)	Pathogenic	C/T	R370W
11575937	14486	NM_170707.4(LMNA):c.1445G>A (p.Arg482Gln)	Pathogenic	G/A	R370Q
57520892	14499	NM_170707.4(LMNA):c.1580G>A (p.Arg527His)	Pathogenic	G/A	R415H
267607592	66853	NM_170707.4(LMNA):c.1608+1G>A	Pathogenic	G/A
267607547	66858	NM_170707.4(LMNA):c.1619T>C (p.Met540Thr)	Pathogenic	T/C	M428T
59886214	14516	NM_170707.4(LMNA):c.1821G>A (p.Val607=)	Pathogenic	G/A
61064130	14501	NM_170707.4(LMNA):c.1822G>A (p.Gly608Ser)	Pathogenic	G/A	G496S
58596362	14500	NM_170707.4(LMNA):c.1824C>T (p.Gly608=)	Pathogenic	C/T
113436208	66879	NM_170707.4(LMNA):c.1968+1G>A	Pathogenic	G/A
	3595598	NM_170707.4(LMNA):c.5del (p.Glu2fs)	Pathogenic	GA/G
59332535	66931	NM_170707.4(LMNA):c.746G>A (p.Arg249Gln)	Pathogenic	G/A	R137Q
59885338	14498	NM_170707.4(LMNA):c.892C>T (p.Arg298Cys)	Pathogenic	C/T	R186C
267607554	48096	NM_170707.4(LMNA):c.961C>T (p.Arg321Ter)	Pathogenic	C/T
797044488	162417	NM_170707.4(LMNA):c.1968+5G>A	Pathogenic/Likely pathogenic	G/A
386134243	36473	NM_170707.4(LMNA):c.1003C>T (p.Arg335Trp)	Likely pathogenic	C/T	R223W
121912493	14520	NM_170707.4(LMNA):c.1318G>A (p.Val440Met)	Likely pathogenic	G/A	V328M
1281896947	561054	NM_170707.4(LMNA):c.1391T>A (p.Met464Lys)	Likely pathogenic	T/A	M352K
57629361	66849	NM_170707.4(LMNA):c.1583C>A (p.Thr528Lys)	Likely pathogenic	C/A	T416K
61444459	66860	NM_170707.4(LMNA):c.1622G>A (p.Arg541His)	Likely pathogenic	G/A	R429H
2102898301	1343751	NM_170707.4(LMNA):c.1646_1647del (p.Val549fs)	Likely pathogenic	CTG/C
2102817930	1308669	NM_170707.4(LMNA):c.164A>G (p.Glu55Gly)	Likely pathogenic	A/G	E55G
2102817952	1341358	NM_170707.4(LMNA):c.168C>G (p.Asn56Lys)	Likely pathogenic	C/G	N56K
918645468	651240	NM_170707.4(LMNA):c.1744C>T (p.Arg582Cys)	Likely pathogenic	C/T	R470C
57830985	14494	NM_170707.4(LMNA):c.1745G>A (p.Arg582His)	Likely pathogenic	G/A	R470H
59601651	66864	NM_170707.4(LMNA):c.1748C>T (p.Ser583Leu)	Likely pathogenic	C/T	S471L
	3899356	NM_170707.4(LMNA):c.175C>G (p.Leu59Val)	Likely pathogenic	C/G	L59V
	3385375	NM_170707.4(LMNA):c.1968G>T (p.Gln656His)	Likely pathogenic	G/T	Q448H
61726475	2572315	NM_170707.4(LMNA):c.331G>A (p.Glu111Lys)	Likely pathogenic	G/A	E111K
199474724	41234	NM_170707.4(LMNA):c.674G>A (p.Arg225Gln)	Likely pathogenic	G/A	R113Q
397517906	48076	NM_170707.4(LMNA):c.725C>T (p.Ala242Val)	Likely pathogenic	C/T	A130V
794728593	200941	NM_170707.4(LMNA):c.768G>A (p.Val256=)	Likely pathogenic	G/A
397517909	1698456	NM_170707.4(LMNA):c.784G>A (p.Glu262Lys)	Likely pathogenic	G/A	E150K
2102883169	1457399	NM_170707.4(LMNA):c.822del (p.Arg275fs)	Likely pathogenic	GC/G
267607591	66952	NM_170707.4(LMNA):c.898G>A (p.Asp300Asn)	Likely pathogenic	G/A	D188N
797045011	208496	NM_170707.4(LMNA):c.936+2T>C	Likely pathogenic	T/C
886045356	292825	NM_005572.3(LMNA):c.-210T>C	Uncertain significance	T/C
886045355	292824	NM_005572.3(LMNA):c.-225C>A	Uncertain significance	C/A
886045354	292823	NM_005572.3(LMNA):c.-226C>T	Uncertain significance	C/T
80338938	66611	NM_005572.4(LMNA):c.1711C>T (p.Arg571Cys)	Uncertain significance	C/T	R490C
1158300738	871955	NM_005572.4(LMNA):c.1715G>A (p.Arg572His)	Uncertain significance	G/A	R491H
886045360	292830	NM_170707.4(LMNA):c.-109G>T	Uncertain significance	G/T
886045359	292828	NM_170707.4(LMNA):c.-138T>C	Uncertain significance	T/C
886045358	292827	NM_170707.4(LMNA):c.-142C>A	Uncertain significance	C/A
886045357	292826	NM_170707.4(LMNA):c.-183C>A	Uncertain significance	C/A
886043355	286271	NM_170707.4(LMNA):c.-1C>A	Uncertain significance	C/A
1185731069	873801	NM_170707.4(LMNA):c.-44T>A	Uncertain significance	T/A
886045362	292833	NM_170707.4(LMNA):c.-5C>A	Uncertain significance	C/A
886045361	292832	NM_170707.4(LMNA):c.-62C>A	Uncertain significance	C/A
370656306	161292	NM_170707.4(LMNA):c.1001G>A (p.Ser334Asn)	Uncertain significance	G/A	S222N
1237093879	923351	NM_170707.4(LMNA):c.1006C>T (p.Arg336Trp)	Uncertain significance	C/T	R224W
58105277	66758	NM_170707.4(LMNA):c.1007G>A (p.Arg336Gln)	Uncertain significance	G/A	R224Q
756538414	2199046	NM_170707.4(LMNA):c.1016C>T (p.Ala339Val)	Uncertain significance	C/T	A227V
749784223	656550	NM_170707.4(LMNA):c.1027C>T (p.Arg343Trp)	Uncertain significance	C/T	R231W
61177390	66759	NM_170707.4(LMNA):c.1028G>A (p.Arg343Gln)	Uncertain significance	G/A	R231Q
1651560077	2977457	NM_170707.4(LMNA):c.1034T>C (p.Met345Thr)	Uncertain significance	T/C	M137T
587777892	155896	NM_170707.4(LMNA):c.1044G>T (p.Met348Ile)	Uncertain significance	G/T	M236I
58789393	2860240	NM_170707.4(LMNA):c.1046G>A (p.Arg349Gln)	Uncertain significance	G/A	R141Q
	3597402	NM_170707.4(LMNA):c.1122C>G (p.His374Gln)	Uncertain significance	C/G	H166Q
267607561	66792	NM_170707.4(LMNA):c.1184C>T (p.Ser395Leu)	Uncertain significance	C/T	S283L
61693978	593242	NM_170707.4(LMNA):c.1187A>T (p.Gln396Leu)	Uncertain significance	A/T	Q284L
747952058	449052	NM_170707.4(LMNA):c.1190G>A (p.Arg397His)	Uncertain significance	G/A	R285H
58672172	14519	NM_170707.4(LMNA):c.1195C>T (p.Arg399Cys)	Uncertain significance	C/T	R287C
267607563	66794	NM_170707.4(LMNA):c.1196G>A (p.Arg399His)	Uncertain significance	G/A	R287H
1206200858	1746556	NM_170707.4(LMNA):c.1198G>A (p.Gly400Ser)	Uncertain significance	G/A	G192S
267607620	1501721	NM_170707.4(LMNA):c.11C>A (p.Pro4Gln)	Uncertain significance	C/A	P4Q
61094188	48035	NM_170707.4(LMNA):c.1201C>T (p.Arg401Cys)	Uncertain significance	C/T	R289C
141490569	287940	NM_170707.4(LMNA):c.1202G>A (p.Arg401His)	Uncertain significance	G/A	R289H
1651615685	925311	NM_170707.4(LMNA):c.1230G>A (p.Gln410=)	Uncertain significance	G/A
727504852	179412	NM_170707.4(LMNA):c.1231G>T (p.Gly411Cys)	Uncertain significance	G/T	G299C
267607647	66796	NM_170707.4(LMNA):c.1232G>A (p.Gly411Asp)	Uncertain significance	G/A	G299D
966050612	965914	NM_170707.4(LMNA):c.1234G>T (p.Gly412Trp)	Uncertain significance	G/T	G300W
766811975	928831	NM_170707.4(LMNA):c.1237G>T (p.Gly413Cys)	Uncertain significance	G/T	G301C
267607606	66797	NM_170707.4(LMNA):c.1243G>A (p.Val415Ile)	Uncertain significance	G/A	V303I
755686359	242002	NM_170707.4(LMNA):c.1255C>T (p.Arg419Cys)	Uncertain significance	C/T	R307C
777648901	476822	NM_170707.4(LMNA):c.1256G>A (p.Arg419His)	Uncertain significance	G/A	R307H
373584456	200943	NM_170707.4(LMNA):c.1279C>T (p.Arg427Cys)	Uncertain significance	C/T	R315C
747139279	245780	NM_170707.4(LMNA):c.1280G>A (p.Arg427His)	Uncertain significance	G/A	R315H
1651628416	948103	NM_170707.4(LMNA):c.1282A>G (p.Ser428Gly)	Uncertain significance	A/G	S316G
1385994420	926754	NM_170707.4(LMNA):c.1286G>A (p.Ser429Asn)	Uncertain significance	G/A	S317N
1651629254	958149	NM_170707.4(LMNA):c.1287C>G (p.Ser429Arg)	Uncertain significance	C/G	S317R
748433620	806244	NM_170707.4(LMNA):c.1300G>A (p.Ala434Thr)	Uncertain significance	G/A	A322T
150840924	66802	NM_170707.4(LMNA):c.1303C>T (p.Arg435Cys)	Uncertain significance	C/T	R323C
876657849	228802	NM_170707.4(LMNA):c.1306A>G (p.Thr436Ala)	Uncertain significance	A/G	T324A
505058	876083	NM_170707.4(LMNA):c.1338T>G (p.Asp446Glu)	Uncertain significance	T/G	D334E
267607598	570103	NM_170707.4(LMNA):c.1358G>A (p.Arg453Gln)	Uncertain significance	G/A	R341Q
397517892	48038	NM_170707.4(LMNA):c.1363C>T (p.Arg455Cys)	Uncertain significance	C/T	R343C
267607597	927247	NM_170707.4(LMNA):c.1364G>A (p.Arg455His)	Uncertain significance	G/A	R343H
372011095	178062	NM_170707.4(LMNA):c.1376A>G (p.Asn459Ser)	Uncertain significance	A/G	N347S
730880133	180405	NM_170707.4(LMNA):c.1381-5G>A	Uncertain significance	G/A
267607642	66819	NM_170707.4(LMNA):c.1381G>T (p.Asp461Tyr)	Uncertain significance	G/T	D349Y
200262654	432879	NM_170707.4(LMNA):c.1390A>G (p.Met464Val)	Uncertain significance	A/G	M352V
11575937	14490	NM_170707.4(LMNA):c.1445G>T (p.Arg482Leu)	Uncertain significance	G/T	R370L
886042993	284948	NM_170707.4(LMNA):c.1453C>G (p.Pro485Ala)	Uncertain significance	C/G	P373A
886042993	3073113	NM_170707.4(LMNA):c.1453C>T (p.Pro485Ser)	Uncertain significance	C/T	P277S
200466188	245964	NM_170707.4(LMNA):c.1487C>T (p.Thr496Met)	Uncertain significance	C/T	T384M
369642101	504326	NM_170707.4(LMNA):c.1488+6T>G	Uncertain significance	T/G
	3598448	NM_170707.4(LMNA):c.1499C>T (p.Ala500Val)	Uncertain significance	C/T	A292V
878855233	242003	NM_170707.4(LMNA):c.1517A>C (p.His506Pro)	Uncertain significance	A/C	H394P
2528011218	3071113	NM_170707.4(LMNA):c.1520G>A (p.Ser507Asn)	Uncertain significance	G/A	S299N
879254163	246227	NM_170707.4(LMNA):c.1529C>T (p.Thr510Ile)	Uncertain significance	C/T	T398I
201583907	48045	NM_170707.4(LMNA):c.1567G>A (p.Gly523Arg)	Uncertain significance	G/A	G411R
144740174	1172352	NM_170707.4(LMNA):c.1601C>G (p.Thr534Ser)	Uncertain significance	C/G	T422S
748917147	476825	NM_170707.4(LMNA):c.1608+10C>T	Uncertain significance	C/T
879253992	245899	NM_170707.4(LMNA):c.161C>T (p.Thr54Met)	Uncertain significance	C/T	T54M
142191737	163878	NM_170707.4(LMNA):c.1634G>A (p.Arg545His)	Uncertain significance	G/A	R433H
1651785654	1025610	NM_170707.4(LMNA):c.1655A>C (p.Asp552Ala)	Uncertain significance	A/C	D440A
373671419	286258	NM_170707.4(LMNA):c.1657G>A (p.Asp553Asn)	Uncertain significance	G/A	D441N
141578711	926250	NM_170707.4(LMNA):c.1664A>G (p.Asp555Gly)	Uncertain significance	A/G	D443G
1057516022	368833	NM_170707.4(LMNA):c.1698+124C>T	Uncertain significance	C/T
555844506	875382	NM_170707.4(LMNA):c.1698+83G>A	Uncertain significance	G/A
	3598524	NM_170707.4(LMNA):c.1699-1_1706dup	Uncertain significance	T/TTCCCAGGGC
1250355311	1329343	NM_170707.4(LMNA):c.1712G>A (p.Ser571Asn)	Uncertain significance	G/A	S459N
60890628	14517	NM_170707.4(LMNA):c.1718C>T (p.Ser573Leu)	Uncertain significance	C/T	S461L
57830985	521983	NM_170707.4(LMNA):c.1745G>T (p.Arg582Leu)	Uncertain significance	G/T	R470L
578193315	476826	NM_170707.4(LMNA):c.1750C>T (p.Arg584Cys)	Uncertain significance	C/T	R472C
56657623	48049	NM_170707.4(LMNA):c.1751G>A (p.Arg584His)	Uncertain significance	G/A	R472H
758048062	487635	NM_170707.4(LMNA):c.1756G>A (p.Val586Met)	Uncertain significance	G/A	V474M
372201662	623706	NM_170707.4(LMNA):c.1765G>A (p.Gly589Arg)	Uncertain significance	G/A	G477R
786205448	190987	NM_170707.4(LMNA):c.1774G>A (p.Gly592Arg)	Uncertain significance	G/A	G480R
2102901580	1284657	NM_170707.4(LMNA):c.1786_1800del (p.Asp596_Ala600del)	Uncertain significance	CCTGCCGACAAGGCAT/C
397517898	48053	NM_170707.4(LMNA):c.1825G>A (p.Gly609Arg)	Uncertain significance	G/A	G497R
	3598590	NM_170707.4(LMNA):c.1840G>T (p.Gly614Cys)	Uncertain significance	G/T	G406C
765594825	567367	NM_170707.4(LMNA):c.1862C>T (p.Thr621Met)	Uncertain significance	C/T	T509M
757888891	289127	NM_170707.4(LMNA):c.1867A>G (p.Thr623Ala)	Uncertain significance	A/G	T511A
13768	66870	NM_170707.4(LMNA):c.1871G>A (p.Arg624His)	Uncertain significance	G/A	R512H
1553266553	518817	NM_170707.4(LMNA):c.1873_1874delinsCC (p.Ser625Pro)	Uncertain significance	AG/CC	S513P
777841827	543199	NM_170707.4(LMNA):c.1879C>T (p.Arg627Cys)	Uncertain significance	C/T	R515C
899373360	1029259	NM_170707.4(LMNA):c.187A>C (p.Ile63Leu)	Uncertain significance	A/C	I63L
745997478	200948	NM_170707.4(LMNA):c.1880G>A (p.Arg627His)	Uncertain significance	G/A	R419H
951584348	640713	NM_170707.4(LMNA):c.1891G>A (p.Gly631Ser)	Uncertain significance	G/A	G519S
2528030504	1924187	NM_170707.4(LMNA):c.1894A>G (p.Ser632Gly)	Uncertain significance	A/G	S424G
1470825986	921458	NM_170707.4(LMNA):c.1901G>A (p.Gly634Asp)	Uncertain significance	G/A	G522D
2527832360	3070790	NM_170707.4(LMNA):c.190A>G (p.Thr64Ala)	Uncertain significance	A/G	T64A
142000963	14527	NM_170707.4(LMNA):c.1930C>T (p.Arg644Cys)	Uncertain significance	C/T	R436C
368386019	161291	NM_170707.4(LMNA):c.1931G>A (p.Arg644His)	Uncertain significance	G/A	R532H
267607544	66877	NM_170707.4(LMNA):c.1960C>T (p.Arg654Ter)	Uncertain significance	C/T
555070042	595804	NM_170707.4(LMNA):c.1968+37C>T	Uncertain significance	C/T
1023544978	1056234	NM_170707.4(LMNA):c.1971C>A (p.Ser657Arg)	Uncertain significance	C/A	S545R
374926367	245639	NM_170707.4(LMNA):c.1978A>G (p.Asn660Asp)	Uncertain significance	A/G	N548D
1329278578	864820	NM_170707.4(LMNA):c.23G>A (p.Arg8His)	Uncertain significance	G/A	R8H
59270054	1518015	NM_170707.4(LMNA):c.244G>C (p.Glu82Gln)	Uncertain significance	G/C	E82Q
794728602	200953	NM_170707.4(LMNA):c.250G>A (p.Glu84Lys)	Uncertain significance	G/A	E84K
1445068583	586127	NM_170707.4(LMNA):c.268A>G (p.Lys90Glu)	Uncertain significance	A/G	K90E
1306829976	860145	NM_170707.4(LMNA):c.272C>T (p.Thr91Ile)	Uncertain significance	C/T	T91I
1553262000	543178	NM_170707.4(LMNA):c.286G>T (p.Ala96Ser)	Uncertain significance	G/T	A96S
1060502216	408995	NM_170707.4(LMNA):c.290A>C (p.Lys97Thr)	Uncertain significance	A/C	K97T
1441670218	925242	NM_170707.4(LMNA):c.293A>G (p.Glu98Gly)	Uncertain significance	A/G	E98G
886045363	292834	NM_170707.4(LMNA):c.294G>A (p.Glu98=)	Uncertain significance	G/A
886045364	292835	NM_170707.4(LMNA):c.295C>A (p.Arg99Ser)	Uncertain significance	C/A	R99S
1649740041	845155	NM_170707.4(LMNA):c.326T>A (p.Val109Glu)	Uncertain significance	T/A	V109E
556237236	522979	NM_170707.4(LMNA):c.329G>A (p.Arg110His)	Uncertain significance	G/A	R110H
1649747809	875747	NM_170707.4(LMNA):c.356+12C>A	Uncertain significance	C/A
1572332952	664101	NM_170707.4(LMNA):c.356+5G>A	Uncertain significance	G/A
397517902	1504530	NM_170707.4(LMNA):c.356G>T (p.Arg119Leu)	Uncertain significance	G/T	R119L
	3596181	NM_170707.4(LMNA):c.394G>T (p.Ala132Ser)	Uncertain significance	G/T	A132S
60864230	200934	NM_170707.4(LMNA):c.398G>A (p.Arg133Gln)	Uncertain significance	G/A	R133Q
	3595738	NM_170707.4(LMNA):c.41C>T (p.Ala14Val)	Uncertain significance	C/T	A14V
760743233	200935	NM_170707.4(LMNA):c.466C>T (p.Arg156Cys)	Uncertain significance	C/T	R156C
764475194	1172290	NM_170707.4(LMNA):c.467G>A (p.Arg156His)	Uncertain significance	G/A	R156H
770799870	1350707	NM_170707.4(LMNA):c.47C>A (p.Ala16Asp)	Uncertain significance	C/A	A16D
1553264647	499012	NM_170707.4(LMNA):c.483G>A (p.Glu161=)	Uncertain significance	G/A
370200334	574040	NM_170707.4(LMNA):c.496C>T (p.Arg166Trp)	Uncertain significance	C/T	R166W
267607570	163866	NM_170707.4(LMNA):c.497G>A (p.Arg166Gln)	Uncertain significance	G/A	R166Q
2527938003	2791821	NM_170707.4(LMNA):c.507G>A (p.Val169=)	Uncertain significance	G/A
1650991296	918198	NM_170707.4(LMNA):c.511A>G (p.Lys171Glu)	Uncertain significance	A/G	K171E
886045365	292836	NM_170707.4(LMNA):c.514-11C>T	Uncertain significance	C/T
267607626	66906	NM_170707.4(LMNA):c.565C>T (p.Arg189Trp)	Uncertain significance	C/T	R108W
766856162	392479	NM_170707.4(LMNA):c.566G>A (p.Arg189Gln)	Uncertain significance	G/A	R108Q
2102878915	1750607	NM_170707.4(LMNA):c.593A>G (p.Gln198Arg)	Uncertain significance	A/G	Q117R
1553265177	519420	NM_170707.4(LMNA):c.610C>G (p.Leu204Val)	Uncertain significance	C/G	L123V
757041809	200964	NM_170707.4(LMNA):c.647G>A (p.Arg216His)	Uncertain significance	G/A	R104H
	3595780	NM_170707.4(LMNA):c.64T>C (p.Ser22Pro)	Uncertain significance	T/C	S22P
370134870	264626	NM_170707.4(LMNA):c.658C>T (p.Arg220Cys)	Uncertain significance	C/T	R108C
1016767319	586128	NM_170707.4(LMNA):c.65C>T (p.Ser22Leu)	Uncertain significance	C/T	S22L
773349450	1677618	NM_170707.4(LMNA):c.689A>G (p.Asp230Gly)	Uncertain significance	A/G	D118G
760388350	853705	NM_170707.4(LMNA):c.692A>G (p.Asn231Ser)	Uncertain significance	A/G	N119S
1195524446	1174962	NM_170707.4(LMNA):c.71C>T (p.Thr24Ile)	Uncertain significance	C/T	T24I
397517907	48078	NM_170707.4(LMNA):c.749C>T (p.Ala250Val)	Uncertain significance	C/T	A138V
61578124	245817	NM_170707.4(LMNA):c.74G>T (p.Arg25Leu)	Uncertain significance	G/T	R25L
1553265346	452332	NM_170707.4(LMNA):c.760G>A (p.Asp254Asn)	Uncertain significance	G/A	D142N
1558129629	574664	NM_170707.4(LMNA):c.762C>A (p.Asp254Glu)	Uncertain significance	C/A	D142E
750246389	518473	NM_170707.4(LMNA):c.787C>A (p.Leu263Met)	Uncertain significance	C/A	L151M
1651418246	874034	NM_170707.4(LMNA):c.796A>G (p.Thr266Ala)	Uncertain significance	A/G	T154A
1553265438	519055	NM_170707.4(LMNA):c.845G>A (p.Ser282Asn)	Uncertain significance	G/A	S170N
765241364	519439	NM_170707.4(LMNA):c.848A>G (p.Asn283Ser)	Uncertain significance	A/G	N171S
746056534	500476	NM_170707.4(LMNA):c.853G>T (p.Val285Leu)	Uncertain significance	G/T	V173L
	3596788	NM_170707.4(LMNA):c.867C>A (p.His289Gln)	Uncertain significance	C/A	H103Q
1651454980	1364459	NM_170707.4(LMNA):c.878A>T (p.Gln293Leu)	Uncertain significance	A/T	Q181L
375987939	652575	NM_170707.4(LMNA):c.886C>T (p.Arg296Cys)	Uncertain significance	C/T	R184C
762653476	579396	NM_170707.4(LMNA):c.893G>T (p.Arg298Leu)	Uncertain significance	G/T	R186L
199881992	292837	NM_170707.4(LMNA):c.936+12C>T	Uncertain significance	C/T
756694090	976132	NM_170707.4(LMNA):c.937-3C>A	Uncertain significance	C/A
267607681	66959	NM_170707.4(LMNA):c.937-7C>G	Uncertain significance	C/G
751707982	222694	NM_170707.4(LMNA):c.937-8C>A	Uncertain significance	C/A
769498020	1329345	NM_170707.4(LMNA):c.940G>A (p.Ala314Thr)	Uncertain significance	G/A	A202T
1212920276	586129	NM_170707.4(LMNA):c.953C>T (p.Ala318Val)	Uncertain significance	C/T	A206V
	3596946	NM_170707.4(LMNA):c.957G>C (p.Lys319Asn)	Uncertain significance	G/C	K111N
56851164	48097	NM_170707.4(LMNA):c.976T>A (p.Ser326Thr)	Uncertain significance	T/A	S214T
745540806	918633	NM_170707.4(LMNA):c.977C>T (p.Ser326Leu)	Uncertain significance	C/T	S214L
1651545788	959267	NM_170707.4(LMNA):c.983C>T (p.Ala328Val)	Uncertain significance	C/T	A216V
775159300	292838	NM_170707.4(LMNA):c.985C>A (p.Arg329Ser)	Uncertain significance	C/A	R217S
775159300	224680	NM_170707.4(LMNA):c.985C>G (p.Arg329Gly)	Uncertain significance	C/G	R217G
397517913	48091	NM_170707.4(LMNA):c.986G>A (p.Arg329His)	Uncertain significance	G/A	R217H
80356803	292829	NM_170707.4(LMNA):c.-128T>C	Likely benign	T/C
115800510	292831	NM_170707.4(LMNA):c.-88G>T	Likely benign	G/T
267607603	66780	NM_170707.4(LMNA):c.1149G>A (p.Glu383=)	Likely benign	G/A
878855232	242001	NM_170707.4(LMNA):c.1155G>A (p.Glu385=)	Likely benign	G/A
757715731	379044	NM_170707.4(LMNA):c.1157+19G>A	Likely benign	G/A
61217436	66801	NM_170707.4(LMNA):c.1299C>T (p.His433=)	Likely benign	C/T
369823958	378088	NM_170707.4(LMNA):c.12G>A (p.Pro4=)	Likely benign	G/A
777846700	669927	NM_170707.4(LMNA):c.1380+18G>A	Likely benign	G/A
750192865	516446	NM_170707.4(LMNA):c.1381-13A>G	Likely benign	A/G
371635492	758400	NM_170707.4(LMNA):c.1381-6C>G	Likely benign	C/G
1651703234	928099	NM_170707.4(LMNA):c.1485G>A (p.Val495=)	Likely benign	G/A
374209100	702959	NM_170707.4(LMNA):c.1488+7G>A	Likely benign	G/A
375516745	292839	NM_170707.4(LMNA):c.1488G>A (p.Thr496=)	Likely benign	G/A
201379016	916768	NM_170707.4(LMNA):c.1489-16C>G	Likely benign	C/G
751886390	513856	NM_170707.4(LMNA):c.153G>T (p.Ser51=)	Likely benign	G/T
41314035	199111	NM_170707.4(LMNA):c.1551G>A (p.Gln517=)	Likely benign	G/A
149339264	48043	NM_170707.4(LMNA):c.1566C>T (p.Cys522=)	Likely benign	C/T
80356812	48044	NM_170707.4(LMNA):c.1584G>A (p.Thr528=)	Likely benign	G/A
748768783	628942	NM_170707.4(LMNA):c.1659C>T (p.Asp553=)	Likely benign	C/T
201936898	386612	NM_170707.4(LMNA):c.1662G>A (p.Glu554=)	Likely benign	G/A
557334569	292840	NM_170707.4(LMNA):c.1698+57G>A	Likely benign	G/A
776616872	924728	NM_170707.4(LMNA):c.1699-9C>T	Likely benign	C/T
776066211	227504	NM_170707.4(LMNA):c.1731T>C (p.Ala577=)	Likely benign	T/C
368581237	378090	NM_170707.4(LMNA):c.1857T>C (p.Ser619=)	Likely benign	T/C
554157057	917027	NM_170707.4(LMNA):c.1968+18dup	Likely benign	C/CT
367938270	923835	NM_170707.4(LMNA):c.369G>A (p.Lys123=)	Likely benign	G/A
11549668	36479	NM_170707.4(LMNA):c.51C>T (p.Ser17=)	Likely benign	C/T
1437725392	1382049	NM_170707.4(LMNA):c.540G>A (p.Lys180=)	Likely benign	G/A
12117552	48071	NM_170707.4(LMNA):c.612G>A (p.Leu204=)	Likely benign	G/A
372962650	383898	NM_170707.4(LMNA):c.811-12C>T	Likely benign	C/T
80356809	48086	NM_170707.4(LMNA):c.811-13T>A	Likely benign	T/A
752558753	263661	NM_170707.4(LMNA):c.927C>A (p.Leu309=)	Likely benign	C/A
775429079	543256	NM_170707.4(LMNA):c.96G>A (p.Lys32=)	Likely benign	G/A
188625872	874656	NM_005572.3(LMNA):c.-223C>T	Benign	C/T
762130433	698186	NM_170707.4(LMNA):c.1227A>G (p.Thr409=)	Benign	A/G
368542816	519022	NM_170707.4(LMNA):c.1324G>A (p.Val442Met)	Benign	G/A	V330M
505058	48037	NM_170707.4(LMNA):c.1338T>C (p.Asp446=)	Benign	T/C
377700689	178061	NM_170707.4(LMNA):c.1488+14C>T	Benign	C/T
4641	48048	NM_170707.4(LMNA):c.1698C>T (p.His566=)	Benign	C/T
513043	192190	NM_170707.4(LMNA):c.357-739T>G	Benign	T/G
41313880	48062	NM_170707.4(LMNA):c.357C>T (p.Arg119=)	Benign	C/T
150645079	200936	NM_170707.4(LMNA):c.471G>A (p.Thr157=)	Benign	G/A
11264444	36480	NM_170707.4(LMNA):c.810+13G>T	Benign	G/T
538089	48088	NM_170707.4(LMNA):c.861T>C (p.Ala287=)	Benign	T/C
267607555	66762	NM_170707.4(LMNA):c.1045C>T (p.Arg349Trp)	Not provided	C/T	R237W
267607552	66817	NM_170707.4(LMNA):c.1380+1G>A	Not provided	G/A
57318642	14487	NM_170707.4(LMNA):c.1579C>T (p.Arg527Cys)	Not provided	C/T	R415C
797044487	162412	NM_170707.4(LMNA):c.1968G>A (p.Gln656=)	Not provided	G/A
60310264	14502	NM_170707.4(LMNA):c.433G>A (p.Glu145Lys)	Not provided	G/A	E145K
61195471	48070	NM_170707.4(LMNA):c.607G>A (p.Glu203Lys)	Not provided	G/A	E122K
267607609	66924	NM_170707.4(LMNA):c.694G>C (p.Gly232Arg)	Not provided	G/C	G120R

Sourced from ^[2]

Mechanism overlap

Shared mechanisms

Shared phenotype terms (HPO) 102

HPO terms annotated to both LMNA and Hutchinson-Gilford Progeria Syndrome.

Abnormal aortic valve morphologyAbnormal mitral valve morphologyAbnormal nasal tip morphologyAbnormal thorax morphologyAbnormally high-pitched voiceAbsence of subcutaneous fatAbsent eyebrowAlopeciaAlopecia totalisAngina pectorisAnkyloglossiaAortic regurgitationAortic valve calcificationAortic valve stenosisAtherosclerosisAvascular necrosisCarotid artery occlusionConductive hearing impairmentCongestive heart failureConvex nasal ridgeCorneal opacityCorneal ulcerationCoxa valgaCraniofacial disproportionCyanosisDecreased serum leptinDelayed eruption of teethDelayed menarcheDental crowdingDermal atrophyDystrophic fingernailsDystrophic toenailEctopic calcificationExertional dyspneaFemale hypogonadismGeneralized abnormality of skinGeneralized osteoporosisGrowth delayHigh palateHigh-frequency sensorineural hearing impairment+ 62 more

Shared pathways 4 pathways

4 Pathway(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Name	Categories	Source
Lamin A processing pathway	disease pathway, signaling pathway	WikiPathways
Influence of laminopathies on Wnt signaling	disease pathway, signaling pathway	WikiPathways
Overlap between signal transduction pathways contributing to LMNA laminopathies	disease pathway	WikiPathways
Progeria-associated lipodystrophy	disease pathway	WikiPathways

Sourced from ^{[8][9][10][11]}

Interventions

Therapeutics

Therapeutic annotations

Lonafarnib Status: Approved · Mechanism: Inhibition · 36 trial(s) · 6 indication(s)

Gene-targeting drugs 1 drugs

1 Drug(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Details	Name	Class	# Indications	# Trials	References
	Lonafarnib	Small Molecule, Synthetic organic	0.00	0.00

Human studies

Clinical trials

6 of 36 trials target this disorder — the rest study LMNA compounds in other indications

Phase I/II Trial of Everolimus in Combination With Lonafarnib in ProgeriaTargets this disorder NCT02579044 · Enrolling by invitation · PHASE2 · 2026-03-27

A Phase 2a, Randomized, Open-Label Study to Determine the Optimal Dose and Evaluate the Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS)Targets this disorder NCT06775041 · Active, not recruiting · PHASE2 · 2026-02-05

An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid LaminopathiesTargets this disorder NCT00916747 · Unknown · PHASE2 · 2023-02-23

A Treatment IND (Investigational New Drug) Protocol for EAP (Expanded Access Program) for the Use of Lonafarnib in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) or Progeroid LaminopathyTargets this disorder NCT03895528 · Approved for marketing · 2021-04-13

A Phase II Pilot Study of Zoledronic Acid, Pravastatin, and Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid LaminopathiesTargets this disorder NCT00879034 · Completed · PHASE2 · 2019-06-11

Clinical trial records 36 records

36 Clinical Trial(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

Accession	Title	Phase	Status	Conditions	Targets Disorder
NCT00081510	A Randomized Double-Blind Phase-2 Study of Anastrozole Plus Lonafarnib (SCH 66336) or Anastrozole Plus Placebo for the Treatment of Subjects With Advanced Breast Cancer	PHASE2	Completed	Breast Cancer	—
NCT00879034	A Phase II Pilot Study of Zoledronic Acid, Pravastatin, and Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathies	PHASE2	Completed	Progeria; Hutchinson-Gilford Syndrome	Yes
NCT02511431	Treatment of Chronic Delta Hepatitis With Lonafarnib and Ritonavir	PHASE2	Completed	Hepatitis D	—
NCT05229991	Once Daily (QD) Dosing of Lonafarnib (LNF) Co-administered With Ritonavir (RTV) for Treatment of Chronic Hepatitis D Virus Infection	PHASE3	Unknown	Hepatitis D, Chronic	—
NCT03719313	A Phase 3, Matrix Design, Partially Double-Blind, Randomized Study of the Efficacy and Safety of 50 mg Lonafarnib/100 mg Ritonavir BID With and Without 180 mcg PEG IFN-alfa-2a for 48 Weeks Compared Wi...	PHASE3	Completed	Hepatitis Delta Virus	—
NCT00068757	Phase I Study of Lonafarnib (SCH66336) in Combination With Herceptin Plus Paclitaxel in HER 2 NEU Overexpressing Breast Cancer	PHASE1	Completed	Breast Cancer	—
NCT02430194	An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With Ritonavir-Boosting +/- Peginterferon Alfa-2a in Patients Chronically Infected With Delta Hepa...	PHASE2	Completed	Chronic Hepatitis D Infection	—
NCT02430181	An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With and Without Ritonavir Boosting in Patients Chronically Infected With Delta Hepatitis (HDV) (L...	PHASE2	Completed	Chronic Hepatitis D Infection	—
NCT02527707	A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of a Titrating-Dose Lonafarnib/Ritonavir in Patients Chronically Infected With Hepatitis Delta V...	PHASE2	Completed	Chronic Delta Hepatitis	—
NCT02968641	A Phase 2b, Open-Label, Randomized Study of the Safety, Tolerability, and Pharmacodynamic Activity of Lonafarnib With or Without Ritonavir in Patients Chronically Infected With Hepatitis Delta Virus (...	PHASE2	Withdrawn	Chronic Delta Hepatitis	—
NCT03600714	Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon	PHASE2	Completed	Liver Disease; Hepatitis D	—
NCT00083096	Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas	PHASE1	Unknown	Brain and Central Nervous System Tumors	—
NCT00102648	Phase I/Ib Study of Sarasar and Temodar in Patients with Recurrent or Temodar-Refractory Glioblastoma Multiforme	PHASE1	Active, not recruiting	Malignant Supratentorial Neoplasm; Recurrent Glioblastoma; Recurrent Gliosarcoma	—
NCT00003956	A Phase I Study of Continuous Oral Administration of SCH 66336 and 5-Fluorouracil/Leucovorin (5FU/LV) in Patients With Advanced Cancer	PHASE1	Completed	Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific	—
NCT00288444	Defining the Interaction of Docetaxel and Lonafarnib in Patients With Advanced Malignancies	PHASE1	Terminated	Lung Cancer; Soft Tissue Sarcoma; Colorectal Carcinoma; Breast Cancer; Prostate Cancer	—
NCT00006351	Phase II Study on SCH 66336 (Farnesyl Protein Transferase Inhibitor) and Gemcitabine as Second Line Treatment in Advanced Metastatic Urothelial Cancer - EORTC Study 16997	PHASE2	Completed	Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Urethral Cancer	—
NCT00020774	A Phase IB Clinical Study Of The Farnesyltransferase Inhibitor SCH 66336 And Gemcitabine In Patients With Resectable Primary Liver Neoplasms	PHASE2	Withdrawn	Liver Cancer	—
NCT00038584	A Phase IB Study of Oral Administration of SCH 66336 Preoperatively in Patients With Head and Neck Squamous Cell Cancer Scheduled for Definitive Therapy	PHASE1	Completed	Carcinoma, Squamous Cell; Cancer of Head and Neck	—
NCT00109538	A Pivotal Randomized Study of Lonafarnib Versus Placebo in the Treatment of Subjects With Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) Who Are Platelet Transfusion Dependen...	PHASE3	Terminated	Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Myelodysplasia; Myelomonocytic	—
NCT00102635	A Phase IB Randomized Translational Study of Fenretinide (4-HPR) in Combination With SCH66336, a Farnesyl Transferase Inhibitor, in Patients With Advanced or Recurrent Head and Neck Cancer	PHASE1	Terminated	Head and Neck Cancer	—
NCT06775041	A Phase 2a, Randomized, Open-Label Study to Determine the Optimal Dose and Evaluate the Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (...	PHASE2	Active, not recruiting	Hutchinson-Gilford Progeria Syndrome	Yes
NCT00038597	Phase II Study of SCH66336, A Farnesyltransferase Inhibitor in Chronic Myelogenous Leukemia (CML)	PHASE2	Completed	Myelogenous Leukemia, Chronic	—
NCT00015899	Phase I Trial Of Escalating Oral Doses Of SCH 66336 In Pediatric Patients With Refractory Or Recurrent Brain Tumors	PHASE1	Completed	Brain and Central Nervous System Tumors	—
NCT00425607	An Open Label Dose Adjusted Phase II Trial of the Oral Farnesyltransferase Inhibitor (FTI) Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathi...	PHASE2	Completed	Progeria; Hutchinson-Gilford Syndrome	Yes
NCT00773474	A Phase II Study of Lonafarnib in Patients With Metastatic Breast Cancer	PHASE2	Terminated	Metastatic Breast Cancer	—
NCT00281515	An Open-label, Multicenter, Randomized Phase II Study to Compare the Effects of Paclitaxel/Carboplatin and Lonafarnib to Those of Paclitaxel/Carboplatin for First-line Treatment of Patients With Epith...	PHASE2	Completed	Epithelial Ovarian Cancer	—
NCT03895528	A Treatment IND (Investigational New Drug) Protocol for EAP (Expanded Access Program) for the Use of Lonafarnib in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) or Progeroid Laminopathy		Approved for marketing	Progeria; HGPS	Yes
NCT01495585	Treatment of Chronic Delta Hepatitis With Lonafarnib	PHASE2	Completed	Hepatitis D	—
NCT00005030	A Phase IB Study of Oral Administration of SCH 66336 Preoperatively in Patients With Colorectal Carcinoma Metastatic to the Liver Scheduled for Exploratory Laparotomy and/or Resection	PHASE1	Withdrawn	Colorectal Cancer; Metastatic Cancer	—
NCT00050336	A Phase 3 Randomized Study of Lonafarnib in Combination With Paclitaxel and Carboplatin vs. Placebo in Combination With Paclitaxel and Carboplatin in Patients With Non-Small Cell Lung Cancer	PHASE3	Terminated	Carcinoma, Non-small-cell Lung; Metastases, Neoplasm	—
NCT00038493	Phase II Evaluation Temozolomide and Farnesyl Transferase Inhibitor (SCH66336) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme	PHASE2	Completed	Glioblastoma Multiforme	—
NCT02579044	Phase I/II Trial of Everolimus in Combination With Lonafarnib in Progeria	PHASE2	Enrolling by invitation	Progeria	Yes
NCT00916747	An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies	PHASE2	Unknown	Progeria	Yes
NCT00539968	An Open-Label, Two-Part Study to Determine the Safety, Tolerability, and Activity of Lonafarnib and Docetaxel	PHASE2	Terminated	Prostate Cancer; Breast Cancer; Ovarian Cancer; Lung Cancer; Gastric Cancer	—
NCT00612651	A Phase I Trial of the Addition of the Farnesyl Transferase Inhibitor, SCH 66336, to Temodar for Patients With Grade 3 and 4 Malignant Gliomas	PHASE1	Completed	Gliosarcoma; Glioblastoma; Anaplastic Astrocytoma	—
NCT00047502	Phase I Study of Lonafarnib (SCH66336) and Gleevec (Imatinib Mesylate) in Chronic Myelogenous Leukemia (CML)	PHASE1	Completed	Chronic Myelogenous Leukemia	—

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Literature

Reading

Shared publications 64 publications

64 Publication(s) for LMNA - Hutchinson-Gilford Progeria Syndrome:

PubMed ID	Title	Year	Journal
30696354	DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations.	2019	Circulation research
29047356	Non-syndromic cardiac progeria in a patient with the rare pathogenic p.Asp300Asn variant in the LMNA gene.	2017	BMC medical genetics
27334370	Novel LMNA mutations cause an aggressive atypical neonatal progeria without progerin accumulation.	2016	Journal of medical genetics
27539898	Increased susceptibility to oxidative stress- and ultraviolet A-induced apoptosis in fibroblasts in atypical progeroid syndrome/atypical Werner syndrome with LMNA mutation.	2016	Experimental dermatology
25649378	Truncated prelamin A expression in HGPS-like patients: a transcriptional study.	2015	European journal of human genetics : EJHG
24623722	Systematic identification of pathological lamin A interactors.	2014	Molecular biology of the cell
24375749	Mapping disease-related missense mutations in the immunoglobulin-like fold domain of lamin A/C reveals novel genotype-phenotype associations for laminopathies.	2014	Proteins
23666920	LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.	2013	American journal of medical genetics. Part A
22611635	Clinical imaging findings in a girl with Hutchinson-Gilford progeria syndrome.	2012	Genetic counseling (Geneva, Switzerland)
21875900	A conserved splicing mechanism of the LMNA gene controls premature aging.	2011	Human molecular genetics
22065502	Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.	2011	American journal of medical genetics. Part A
20458013	Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging.	2010	Circulation
20079404	Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins.	2010	Biochimica et biophysica acta
20044904	Evidence for the involvement of lamins in aging.	2010	Current aging science
19172989	Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin A transcript during cell aging.	2009	European journal of human genetics : EJHG
19875478	Atypical progeroid syndrome due to heterozygous missense LMNA mutations.	2009	The Journal of clinical endocrinology and metabolism
19680556	Genetic variation in healthy oldest-old.	2009	PloS one
19283854	Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.	2009	American journal of medical genetics. Part A
19842191	Progeroid syndrome with scleroderma-like skin changes associated with homozygous R435C LMNA mutation.	2009	American journal of medical genetics. Part A
19432833	Homozygous LMNA mutation R527C in atypical Hutchinson-Gilford progeria syndrome: evidence for autosomal recessive inheritance.	2009	Acta paediatrica (Oslo, Norway : 1992)
19938095	Absence of Lamin A/C gene mutations in four Wiedemann-Rautenstrauch syndrome patients.	2009	American journal of medical genetics. Part A
19727227	Association of progerin-interactive partner proteins with lamina proteins: Mel18 is associated with emerin in HGPS.	2009	Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
17870066	Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A.	2008	Experimental cell research
18478590	Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.	2008	American journal of medical genetics. Part A
18366013	Lamin A/C, laminopathies and premature ageing.	2008	Histology and histopathology
18442998	Epidermal expression of the truncated prelamin A causing Hutchinson-Gilford progeria syndrome: effects on keratinocytes, hair and skin.	2008	Human molecular genetics
18348272	Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.	2008	American journal of medical genetics. Part A
19014358	Microcephalia with mandibular and dental dysplasia in adult Zmpste24-deficient mice.	2008	Journal of anatomy
18339564	Progeria caused by a rare LMNA mutation p.S143F associated with mild myopathy and atrial fibrillation.	2008	European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
18564364	Laminopathies in Russian families.	2008	Clinical genetics
17469202	Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.	2007	Human mutation
18646565	Emerinopathy and laminopathy clinical, pathological and molecular features of muscular dystrophy with nuclear envelopathy in Japan.	2007	Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
17618517	An association of Hutchinson-Gilford progeria and malignancy.	2007	American journal of medical genetics. Part A
17459035	Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature.	2007	The British journal of dermatology
17718387	[The role of lamins and mutations of LMNA gene in physiological and premature aging].	2007	Postepy biochemii
17556535	The retinol acid receptor B gene is hypermethylated in patients with familial partial lipodystrophy.	2007	Journal of molecular endocrinology
16738054	Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging.	2006	Proceedings of the National Academy of Sciences of the United States of America
16478798	Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration.	2006	Brain : a journal of neurology
16965317	The laminopathies: a clinical review.	2006	Clinical genetics
17090536	Prelamin A farnesylation and progeroid syndromes.	2006	The Journal of biological chemistry
16825282	Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation.	2006	Human molecular genetics
16671095	A homozygous ZMPSTE24 null mutation in combination with a heterozygous mutation in the LMNA gene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS.	2006	Human mutation
16278265	A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.	2006	The Journal of clinical endocrinology and metabolism
16920618	Aging: progeria and the lamin connection.	2006	Current biology : CB
16126733	Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition.	2005	Human molecular genetics
16186497	Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome.	2005	Proceedings of the National Academy of Sciences of the United States of America
16061563	In vivo and in vitro examination of the functional significances of novel lamin gene mutations in heart failure patients.	2005	Journal of medical genetics
16208517	Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference.	2005	Human genetics
15622532	p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria.	2005	Annals of neurology
15793835	Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.	2005	American journal of medical genetics. Part A
16550925	X-linked form of Emery-Dreifuss muscular dystrophy.	2005	Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
15184648	Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.	2004	Proceedings of the National Academy of Sciences of the United States of America
14755334	Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.	2004	The Journal of clinical investigation
15317753	Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy.	2004	Human molecular genetics
15479179	Hutchinson-Gilford progeria syndrome.	2004	Clinical genetics
15121795	LMNA mutation in a 45 year old Japanese subject with Hutchinson-Gilford progeria syndrome.	2004	Journal of medical genetics
15205220	Laminopathies and atherosclerosis.	2004	Arteriosclerosis, thrombosis, and vascular biology
15342704	Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.	2004	Journal of medical genetics
15032975	Paternal origin of LMNA mutations in Hutchinson-Gilford progeria.	2004	Clinical genetics
12714972	Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.	2003	Nature
12768443	LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).	2003	Journal of human genetics
14684700	Mutation analysis of the lamin A/C gene (LMNA) among patients with different cardiomuscular phenotypes.	2003	Journal of medical genetics
14675861	Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation.	2003	European journal of heart failure
11799477	Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.	2002	American journal of human genetics

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