期刊
HUMAN MUTATION
卷 35, 期 8, 页码 915-926出版社
WILEY-HINDAWI
DOI: 10.1002/humu.22583
关键词
GNE; distal myopathy with rimmed vacuoles; DMRV; hereditary inclusion body myopathy; HIBM; adult onset muscular dystrophy
资金
- Intramural Research Program of the National Human Genome Research Institute (NHGRI)
- Therapeutics for Rare and Neglected Diseases (TRND) Program of the National Center for Advancing Translational Sciences (NCATS)
- National Institutes of Health, Bethesda, Maryland, United States
The GNE gene encodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). Biallelic GNE mutations underlie GNE myopathy, an adult-onset progressive myopathy. GNE myopathy-associated GNE mutations are predominantly missense, resulting in reduced, but not absent, GNE enzyme activities. The exact pathomechanism of GNE myopathy remains unknown, but likely involves aberrant (muscle) sialylation. Here, we summarize 154 reported and novel GNE variants associated with GNE myopathy, including 122 missense, 11 nonsense, 14 insertion/deletions, and seven intronic variants. All variants were deposited in the online GNE variation database (http://www.dmd.nl/nmdb2/home.php?select_db=GNE). We report the predicted effects on protein function of all variants well as the predicted effects on epimerase and/or kinase enzymatic activities of selected variants. By analyzing exome sequence databases, we identified three frequently occurring, unreported GNE missense variants/polymorphisms, important for future sequence interpretations. Based on allele frequencies, we estimate the world-wide prevalence of GNE myopathy to be similar to 4-21/1,000,000. This previously unrecognized high prevalence confirms suspicions that many patients may escape diagnosis. Awareness among physicians for GNE myopathy is essential for the identification of new patients, which is required for better understanding of the disorder's pathomechanism and for the success of ongoing treatment trials. Published 2014 Wiley Periodicals, Inc.**
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