title: Novel GNE mutations in hereditary inclusion body myopathy patients of non-Middle Eastern descent.
abstract: Autosomal recessive hereditary inclusion body myopathy (HIBM or IBM2) is a progressive adult onset muscle wasting disorder characterized by sparing of the quadriceps. IBM2 is also known as distal myopathy with rimmed vacuoles or nonaka myopathy. IBM2 is associated with mutations in the UDP-GlcNAc 2-Epimerase/ManNAc Kinase gene (GNE). GNE is the rate-limiting enzyme of N-Acetylneuraminate (Neu5Ac, Sialic acid) biosynthesis. The GNE coding region of 64 symptomatic patients were sequenced. Twenty-eight patients were found to bear GNE mutations. Ten novel mutations were identified among nine patients, including four nonsense (p.R8X, p.W204X, p.Q436X, and p.S615X) and five missense (p.R71W, p.I142T, p.I298T, p.L556S, and p.E2G) variations spanning both the epimerase and kinase domains of GNE. Additionally, a synonymous variation (p.Y591Y, codon tac > tat) was seen in a patient bearing compound heterozygous nonsynonymous mutations (p.S615X and p.Y675H). Six of the nine are Caucasian, one patient is Taiwanese, one patient is Asian Indian, and one patient is of European descent. These findings further expand the clinical and genetic spectrum of IBM2.
authors.affiliation: HIBM Research Group, Los Angeles, California 91335, USA. chai@hibm.org
authors.forename: Chai
authors.initials: C
authors.lastname: Saechao
authors.forename: Yadira
authors.initials: Y
authors.lastname: Valles-Ayoub
authors.forename: Saghi
authors.initials: S
authors.lastname: Esfandiarifard
authors.forename: Arman
authors.initials: A
authors.lastname: Haghighatgoo
authors.forename: Daniel
authors.initials: D
authors.lastname: No
authors.forename: Steven
authors.initials: S
authors.lastname: Shook
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
authors.forename: Xiomara
authors.initials: X
authors.lastname: Rosales-Quintero
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Felice
authors.forename: Chantal F
authors.initials: CF
authors.lastname: Morel
authors.forename: Marvin
authors.initials: M
authors.lastname: Pietruska
authors.forename: Daniel
authors.initials: D
authors.lastname: Darvish
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D049310:Distal Myopathies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D019683:Penetrance; D017434:Protein Structure, Tertiary
chemical_list: D018389:Codon, Nonsense; D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase