Résumé :
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Communication n° 522 Hereditary Inclusion Body Myopathy (HIBM) is a recessive autosomal disorder which has been related in 2001 to mutations in the GNE gene. Clinically, the disorder is slowly progressive, with adult onset and is characterized by distal and proximal symmetrical muscle weakness and wasting of upper and lower limbs, typically sparing the quadriceps. Muscle pathology shows rimmed vacuoles and filamentous inclusions. Nonaka autosomal recessive myopathy (or distal myopathy with rimmed vacuoles) is also caused by mutations in GNE and is thus an allelic disorder. The UDP-N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase (GNE) gene is located in 9p12-13 and encodes an ubiquitously expressed protein involved in the biosynthesis of N-acetyl neuraminic acid. We have performed the molecular exploration of the gene, for help in diagnosis and genetic counselling, in a first serie of 18 unrelated patients selected on clinical basis and histological criteria from muscular biopsy. The 11 coding exons of the gene have been screened by DHPLC and sequence analysis in case of heteroduplex pattern. Familial exploration was perfomed secondarly on available samples. We thus identified 12 sequence variations; 11 were missense mutations, of which only 4 have been previously reported. All mutated patients (7 of 18) were homozygous or compound heterozygous, no single heterozygous mutations was identified in affected individuals. When performed, segregation analysis was consistent with recessive transmission and causality of the mutations identified. In one family we identified 3 sequence variations always present in the 6 affected individuals, two unpublished missense mutations and one nucleotide change predicted to be neutral at the protein level. Further investigations would therefore be necessary to interpret the molecular results in this family. Available phenotypic data of the 18 tested patients are reviewed in regard of our molecular results.
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