Megaconial congenital muscular dystrophy due to loss-of-function mutations in choline kinase β.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Neuromuscular Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan.
Satomi
S
Mitsuhashi
Ichizo
I
Nishino
D000818:Animals; D002797:Choline Kinase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics*; D009136:Muscular Dystrophies / Q000151:congenital / Q000201:enzymology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
C542592:CHKB protein, human; D002797:Choline Kinase