Abstract:

PURPOSE OF REVIEW: Recessive mutations in CHKB cause a megaconial congenital muscular dystrophy whose most characteristic feature is mitochondrial enlargement at the periphery of muscle fibers and loss of mitochondria in the center of muscle fibers. This review will summarize clinicopathological features, genetic cause, and biochemical abnormalities of the disease, trying to decipher the mechanism of this complex disorder.
RECENT FINDINGS: Since our report of CHKB mutations found in 15 cases with megaconial congenital muscular dystrophy from Japanese, Turkish, and British populations, we have further identified two British and one French patients. One African-American patient has also been reported by another group. All patients have relatively homogenous phenotype although severity varies to some extent. The peculiar distribution pattern of enlarged mitochondria on muscle section seems to be due to a compensatory mechanism after the elimination of functionally defective mitochondria by mitophagy.
SUMMARY: CHKB encodes choline kinase β, an enzyme that catalyzes the first de-novo biosynthetic step of phosphatidylcholine, the most abundant phospholipid in the eukaryotic membrane. The identification of a new muscle disease caused by the defect in phospholipid metabolism will pave the way for a novel biological pathway that connects phospholipid metabolism, mitochondria biology, and muscular dystrophy.

日本語要旨:

コリンキナーゼベータ遺伝子の機能喪失変異はミトコンドリア巨大化を伴う先天性筋ジストロフィーを引き起こす。これまでに19例の患者が報告されており、皮膚症状を示す症例や軽少例など、臨床症状が比較的多彩であることがわかってきている。これまでに報告されている変異と臨床像のまとめ、および考えられる病気の発症メカニズムについて解説する。