Novel GNE Mutations in Autosomal Recessive Hereditary Inclusion Body Myopathy Patients

作者：No Daniel; Valles Ayoub Yadira^*; Carbajo Rosangela; Khokher Zeshan; Sandoval Lucia; Stein Beth; Tarnopolsky Mark Andrew; Mozaffar Tahseen; Darvish Babak; Pietruszka Marvin; Darvish Daniel

来源：Genetic Testing and Molecular Biomarkers, 2013, 17(5): 376-382.

DOI：10.1089/gtmb.2012.0408

Hereditary Inclusion Body Myopathy (HIBM, IBM2, MIM:600737) is an autosomal recessive adult onset progressive muscle wasting disorder. It is associated with the degeneration of distal and proximal muscles, while often sparing the quadriceps. The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK), encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneunaminic acid (sialic acid). Affected individuals have been identified with mutations in the GNE gene. In the present study, the GNE coding region of 136 symptomatic patients were sequenced. A total of 41 patients were found to have GNE mutations. Eight novel mutations were discovered among seven patients. Of the eight novel mutations, seven were missense (p.I150V, p.Y186C, p.M265T, p.V315T, p.N317D, p.G669R, and p.S699L) and one was nonsense (p.W495X), all of which span the epimerase, kinase, and allosteric domains of GNE. In one patient, one novel mutation was found in the allosteric region and kinase domain of the GNE gene. Mutations in the allosteric region lead to a different disease, sialuria; however, this particular mutation has not been described in patients with sialuria. The pathological significance of this variation with GNE function remains unknown and further studies are needed to identify its connection with HIBM. These findings further expand the clinical and genetic spectrum of HIBM.

• 出版日期2013-5