Mutations spectrum ofGNE in hereditary inclusion body myopathy sparing the quadriceps

作者：Iris Eisenberg, Gil Grabov-Nardini, Hagit Hochner, Mira Korner, Menachem Sadeh, Tulio E. Bertorini, Kate M. D. Bushby, Claudio C. Castellan, Kevin J. Felice, Jerry R. Mendell, Luciano Merlini, Christopher J. Shilling, Itshak Wirguin, Zohar Argov, Stella Mitrani‐Rosenbaum · 发表于：Human Mutation · 年份：2002 · DOI：10.1002/humu.9100 · 被引用次数：118 · 研究领域：Inflammatory Myopathies and Dermatomyositis、Cardiomyopathy and Myosin Studies、Protein Kinase Regulation and GTPase Signaling

Hereditary Inclusion Body Myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult onset and a typical muscle pathology. We have recently identified the gene encoding for a bifunctional enzyme, UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE), as the mutated gene in the prototype form of the disease presenting quadriceps sparing, particularly common in Middle Eastern Jews. Interestingly, we have identified the homozygous M712T Middle Eastern Jewish mutation also in two unrelated Middle Eastern Moslem families. We have also evaluated the involvement of GNE in several families from worldwide non-Jewish ethnic origins presenting symptoms similar to the Middle Eastern HIBM prototype. A total of 14 GNE mutations were identified (one nonsense and 13 missense), of which six are novel: an homozygous missense mutation in a consanguineous family from Italy and in a non consanguineous family from USA, and distinct compound heterozygotes in families from Germany, Italy, Ireland, Bahamas, USA and East India. This study brings to 17 the number of reported GNE mutations in quadriceps sparing myopathy, occurring either in the epimerase or the kinase domain of the enzyme. The mechanism leading to this unique phenotype still remains to be elucidated.