Abstract:

BACKGROUND: Missense mutations in dynamin 2 gene (DNM2) are associated with autosomal dominant centronuclear myopathy (CNM) with characteristic histopathological findings of centrally located myonuclei in a large number of muscle fibers.
METHODS: To identify Japanese CNM caused by DNM2 mutations (DNM2-CNM), we sequenced DNM2 in 22 unrelated Japanese patients who were pathologically diagnosed with CNM. The clinical and pathological findings of DNM2-CNM in patients were reviewed.
RESULTS: We identified 3 different heterozygous missense mutations (p.E368K, p.R369W, and p.R465W) in 4 probands from 4 families. Clinically, calf muscle atrophy and pes cavus are features that are highly suggestive of DNM2-CNM among all CNMs. Pathologically, all 4 DNM2-CNM patients showed a radial distribution of myofibrils in scattered fibers, type 1 fiber atrophy, type 1 fiber predominance, and type 2C fibers. None of the non-DNM2-CNM patients exhibited all the 4 abovementioned pathological features, although some patients showed radial distribution without type 1 fiber atrophy and/or type 2C fibers.
DISCUSSION: These results indicate that the clinicopathological features of DNM2-CNM are rather homogeneous and can be distinguished from the features of non-DNM2-CNM.

日本語要旨:

血縁関係のない22名の日本人中心核ミオパチー患者についてDMN2遺伝子解析を行った。その結果、p,E368K, p,R369W, p,R465Wの3つ変異が4家系で見出された。DNM2変異を有する患者では、下腿後面筋萎縮と凹足が特徴的であった。病理学的には、放射状の筋原線維配列、タイプ1線維萎縮、タイプ1線維優位、タイプ2C線維が認められた。