Molecular genetics and metabolism

Four novel mutations associated with autosomal recessive inclusion body myopathy (MIM: 600737).

PMID 12409274


Recently, mutations in the gene encoding for the bi-functional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), symbol GNE or GLCNE (MIM: 603824) [EC], were associated with IBM2 (MIM: 600737). IBM2 is a recessively inherited vacuolar myopathy with a prevalence rate of 1-2/1000 amongst people of Iranian-Jewish descent. Seven missense mutations were previously described by Eisenberg et al. All families tested from Iranian and Middle Eastern Jewish ancestry have the same homozygous mutation (bp2186t>c). Here we review the mutations in GNE associated with IBM2, and we describe additional four mutations found in individuals suffering from clinically similar disorder who are not of Iranian or Jewish descent. These findings further confirm that homozygous or compound heterozygous mutations of GNE/MNK gene associated with IBM2 are not confined to any single specific region of the enzyme outside its negative feedback regulatory domain located at codons 249-275.