Abstract:

Mutations in the multiple epidermal growth factor-like domains 10 (MEGF10: NM_032446.2) gene are known to cause early-onset myopathy characterized by areflexia, respiratory distress, and dysphagia (EMARDD: OMIM 614399), and a milder phenotype of minicore myopathy. To date, there have been reports of six families with EMARDD and one with a milder disorder. Cysteine mutations in the extracellular EGF-like domain may be responsible for the milder phenotype, but the relationship is not conclusive because of the few reports of this disorder. We here present two Japanese patients with MEGF10 mutations: one with EMARDD phenotype who had a novel homozygous frameshift mutation, c.131_132del, and the other with the milder phenotype who harbored a compound heterozygous mutation, c.2981-2A > G, and a novel missense mutation, p.Cys810Tyr. This is the first report on East Asian patients with MEGF10 myopathy showing two phenotypes, indicating the genotype-phenotype correlation in MEGF10 myopathy.

日本語要旨:

Multiple epidermal growth factor-like domeins(MEGF10)遺伝子の変異は、重症な腱反射消失、呼吸障害、嚥下障害を伴う早期発症型ミオパチー(EMARDD)と、比較的軽症なミニコアミオパチーの二つの表現型が報告されている。我々は、日本人患者でMEGF10遺伝子の変異によるEMARDDとミニコアミオパチーをそれぞれ発見し、遺伝子型と表現型の相関について考察を行った。これは、東アジアで初めてのMEGF10ミオパチーの報告である。