Reviewed April 2011
What is the official name of the LMNA gene?
The official name of this gene is “lamin A/C.”
LMNA is the gene's official symbol. The LMNA gene is also known by other names, listed below.
What is the normal function of the LMNA gene?
The LMNA gene provides instructions for making several slightly different proteins called lamins. The two major proteins produced from this gene, lamin A and lamin C, are made in most of the body's cells. These proteins have a nearly identical sequence of protein building blocks (amino acids). The small difference in the sequence makes lamin A longer than lamin C.
Lamins A and C are structural proteins called intermediate filament proteins. Intermediate filaments provide stability and strength to cells. Lamins A and C are essential scaffolding (supporting) components of the nuclear envelope, which is a structure that surrounds the nucleus in cells. Specifically, these proteins are located in the nuclear lamina, a mesh-like layer of intermediate filaments that is attached to the inner membrane of the nuclear envelope. The nuclear envelope regulates the movement of molecules into and out of the nucleus, and researchers believe it may play a role in regulating the activity (expression) of certain genes.
The lamin A protein must be processed within the cell before becoming part of the lamina. Its initial form, called prelamin A, undergoes a complex series of steps that are necessary for the protein to be inserted into the lamina. Lamin C does not have to undergo this processing before becoming part of the lamina.
How are changes in the LMNA gene related to health conditions?
- Charcot-Marie-Tooth disease - caused by mutations in the LMNA gene
At least one LMNA gene mutation has been identified in people with a form of Charcot-Marie-Tooth disease known as type 2B1. The mutation changes a single amino acid in the LMNA proteins. Specifically, the amino acid arginine is replaced by the amino acid cysteine at protein position 298 (written as Arg298Cys or R298C). Although its effect is not fully understood, the Arg298Cys mutation alters a protein region important for interactions with other molecules. It is unclear how the altered LMNA proteins contribute to the signs and symptoms of type 2B1 Charcot-Marie-Tooth disease.
- Emery-Dreifuss muscular dystrophy - caused by mutations in the LMNA gene
More than 100 mutations in the LMNA gene have been identified in people with Emery-Dreifuss muscular dystrophy. Most of these mutations change single amino acids in lamins A and C, which alters the structure of these proteins. The effect of LMNA mutations within cells remains unclear. Abnormal versions of lamins A and C may alter the activity of certain genes or weaken the structure of the nucleus, making cells more fragile. Researchers continue to investigate how LMNA mutations affect muscles used for movement (skeletal muscles) and heart (cardiac) muscle, leading to the characteristic features of Emery-Dreifuss muscular dystrophy.
- Hutchinson-Gilford progeria syndrome - caused by mutations in the LMNA gene
A specific mutation in the LMNA gene has been found in most patients with Hutchinson-Gilford progeria syndrome. This mutation changes a single DNA building block (nucleotide) in the gene. Specifically, the mutation replaces the nucleotide cytosine with the nucleotide thymine at position 1824 (written as C1824T). This mutation is also sometimes noted as Gly608Gly or G608G, which refers to the position in the lamin A protein affected by the mutation. The C1824T mutation leads to an abnormal version of the lamin A protein called progerin, which is missing 50 amino acids near one end. The location of this mutation does not affect the production of lamin C. Other mutations in the LMNA gene have been identified in a small number of people with the features of Hutchinson-Gilford progeria syndrome.
The mutations responsible for this disorder result in an abnormal version of lamin A that cannot be processed correctly within the cell. When the altered protein is incorporated into the lamina, it can disrupt the shape of the nuclear envelope. Over time, a buildup of this altered protein appears to damage the structure and function of the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the signs and symptoms of Hutchinson-Gilford progeria syndrome.
- limb-girdle muscular dystrophy - caused by mutations in the LMNA gene
At least six mutations in the LMNA gene have been identified in people with limb-girdle muscular dystrophy type 1B. Limb-girdle muscular dystrophy is a group of related disorders characterized by muscle weakness and wasting, particularly in the shoulders, hips, and limbs.
LMNA gene mutations that cause limb-girdle muscular dystrophy may impair the function of lamin proteins. Impaired lamin protein function may lead to a fragile, easily-damaged cell nucleus or improperly regulated genes that affect a variety of cell activities. It is not known how the effects of LMNA gene mutations relate to the specific signs and symptoms of limb-girdle muscular dystrophy.
- other disorders - caused by mutations in the LMNA gene
Mutations in the LMNA gene have been found to cause several other inherited conditions. Because the conditions result from mutations that affect lamin proteins, they are known as laminopathies. Familial dilated cardiomyopathy with conduction defects has severe effects on cardiac muscle that result in life-threatening heart problems. The features of this disorder, and also those of limb-girdle muscular dystrophy type 1B, overlap with those of the autosomal dominant form of Emery-Dreifuss muscular dystrophy. Because certain LMNA mutations may be responsible for any of these conditions, researchers suspect that limb-girdle muscular dystrophy type 1B and familial dilated cardiomyopathy with conduction defects may be variants of Emery-Dreifuss muscular dystrophy instead of separate disorders.
Other laminopathies affect the amount and distribution of fat in the body. Dunnigan type partial lipodystrophy is characterized by a loss of fatty tissue from the trunk and limbs, and a buildup of fat around the neck and shoulders. Mandibuloacral dysplasia also alters the distribution of fatty tissue and causes abnormalities in some bones, particularly in the jaw, hands, and feet.
Mutations in the LMNA gene have been identified in newborns with a disorder called lethal restrictive dermopathy. Infants with this disorder have tight, rigid skin; underdeveloped lungs; and other abnormalities. They do not usually survive past the first week of life.
Researchers have not determined how mutations in the LMNA gene result in this diverse group of disorders, but the multiple roles of the nuclear lamina in cells may help explain the wide variety of signs and symptoms.
Where is the LMNA gene located?
Cytogenetic Location: 1q22
Molecular Location on chromosome 1: base pairs 156,052,368 to 156,109,879
The LMNA gene is located on the long (q) arm of chromosome 1 at position 22.
More precisely, the LMNA gene is located from base pair 156,052,368 to base pair 156,109,879 on chromosome 1.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about LMNA?
You and your healthcare professional may find the following resources about LMNA helpful.
Educational resources - Information pages
- Madame Curie Bioscience Database: Laminopathies: One Gene, Two Proteins, Five Diseases... (http://www.ncbi.nlm.nih.gov/books/NBK6151/)
- University of Washington Neuromuscular Disease Center (http://neuromuscular.wustl.edu/musdist/lg.html)
Gene Reviews - Clinical summary
- Gene Review: Charcot-Marie-Tooth Neuropathy Type 2 (http://www.ncbi.nlm.nih.gov/books/NBK1285/)
- Gene Review: Congenital Muscular Dystrophy (http://www.ncbi.nlm.nih.gov/books/NBK1291/)
- Gene Review: Dilated Cardiomyopathy (http://www.ncbi.nlm.nih.gov/books/NBK1309/)
- Gene Review: Emery-Dreifuss Muscular Dystrophy (http://www.ncbi.nlm.nih.gov/books/NBK1436/)
- Gene Review: Hutchinson-Gilford Progeria Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1121/)
- Gene Review: Limb-Girdle Muscular Dystrophy (http://www.ncbi.nlm.nih.gov/books/NBK1408/)
- Gene Review: LMNA-Related Dilated Cardiomyopathy (http://www.ncbi.nlm.nih.gov/books/NBK1674/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for LMNA (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4000%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((LMNA%5BTIAB%5D)%20OR%20(lamin%20A/C%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- CARDIOMYOPATHY, DILATED, 1A (http://omim.org/entry/115200)
- LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2 (http://omim.org/entry/151660)
- LAMIN A/C (http://omim.org/entry/150330)
- MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY (http://omim.org/entry/248370)
- RESTRICTIVE DERMOPATHY, LETHAL (http://omim.org/entry/275210)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_LMNA.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4000)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4000)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=6636)
- Inherited Peripheral Neuropathies Mutation Database (http://www.molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?Context=21)
- Leiden University Medical Center: Lamin A/C (LMNA) sequence variations (http://www.dmd.nl/nmdb/home.php?select_db=LMNA)
What other names do people use for the LMNA gene or gene products?
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding LMNA?
amino acid ;
autosomal dominant ;
cell nucleus ;
fatty tissue ;
intermediate filaments ;
muscular dystrophy ;
nuclear envelope ;
You may find definitions for these and many other terms in the Genetics Home Reference
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The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.