title: Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps.
abstract: 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.
authors.affiliation: Molecular Biology Unit, Hadassah Hospital, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Eisenberg
authors.forename: Gil
authors.initials: G
authors.lastname: Grabov-Nardini
authors.forename: Hagit
authors.initials: H
authors.lastname: Hochner
authors.forename: Mira
authors.initials: M
authors.lastname: Korner
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.forename: Tulio
authors.initials: T
authors.lastname: Bertorini
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Claudio
authors.initials: C
authors.lastname: Castellan
authors.forename: Kevin
authors.initials: K
authors.lastname: Felice
authors.forename: Jerry
authors.initials: J
authors.lastname: Mendell
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Christopher
authors.initials: C
authors.lastname: Shilling
authors.forename: Itshak
authors.initials: I
authors.lastname: Wirguin
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.forename: Stella
authors.initials: S
authors.lastname: Mitrani-Rosenbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D002238:Carbohydrate Epimerases / Q000235:genetics*; D004252:DNA Mutational Analysis; D029968:Escherichia coli Proteins; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*
chemical_list: D029968:Escherichia coli Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; C083982:wecB protein, E coli