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The official name of this gene is “like-glycosyltransferase.”
LARGE is the gene's official symbol. The LARGE gene is also known by other names, listed below.
The LARGE gene provides instructions for making a protein that is involved in a process called glycosylation. Through this chemical process, sugar molecules are added to certain proteins. In particular, the LARGE protein adds chains of sugar molecules composed of xylose and glucuronic acid to a protein called alpha (α)-dystroglycan. Glycosylation is critical for the normal function of α-dystroglycan.
The α-dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, glycosylated α-dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.
The LARGE gene belongs to a family of genes called glycosyltransferase family 8 domain containing (glycosyltransferase family 8 domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
Mutations in the LARGE gene cause Walker-Warburg syndrome in a small number of individuals. This condition is the most severe form of a group of disorders known as congenital muscular dystrophies. Walker-Warburg syndrome causes muscle weakness and abnormalities of the brain and eyes. Because of the severity of the problems caused by this condition, affected individuals usually do not survive past early childhood.
LARGE gene mutations involved in Walker-Warburg syndrome prevent the normal glycosylation of α-dystroglycan. As a result, α-dystroglycan can no longer effectively anchor cells to the proteins and other molecules that surround them. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, which affects the development, structure, and function of skeletal muscles in people with Walker-Warburg syndrome.
Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead appears bumpy and irregular. Less is known about the effects of LARGE gene mutations on other parts of the body.
Mutations in the LARGE gene are also involved in a less severe form of congenital muscular dystrophy known as congenital muscular dystrophy type 1D (MDC1D). This condition causes muscle weakness, brain abnormalities, and intellectual disability but does not affect the eyes. As in Walker-Warburg syndrome (described above), LARGE gene mutations that cause MDC1D prevent the normal glycosylation of α-dystroglycan. It is unclear how mutations in this gene cause a range of muscular dystrophies.
Cytogenetic Location: 22q12.3
Molecular Location on chromosome 22: base pairs 33,272,522 to 33,920,475
The LARGE gene is located on the long (q) arm of chromosome 22 at position 12.3.
More precisely, the LARGE gene is located from base pair 33,272,522 to base pair 33,920,475 on chromosome 22.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about LARGE helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
cell ; congenital ; cytoskeleton ; disability ; extracellular ; extracellular matrix ; gene ; glycosylation ; muscle cells ; muscular dystrophy ; neuronal migration ; protein ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.