A Congenital Muscular Dystrophy with Mitochondrial Structural Abnormalities Caused by Defective De Novo Phosphatidylcholine Biosynthesis

作者：Mitsuhashi Satomi; Ohkuma Aya; Talim Beril; Karahashi Minako; Koumura Tomoko; Aoyama Chieko; Kurihara Mana; Quinlivan Ros; Sewry Caroline; Mitsuhashi Hiroaki; Goto Kanako; Koksal Burcu; Kale Gulsev; Ikeda Kazutaka; Taguchi Ryo; Noguchi Satoru; Hayashi Yukiko K; Nonaka Ikuya; Sher Roger B; Sugimoto Hiroyuki; Nakagawa Yasuhito; Cox Gregory A; Topaloglu Haluk; Nishino Ichizo^*

来源：American Journal of Human Genetics, 2011, 88(6): 845-851.

DOI：10.1016/j.ajhg.2011.05.010

Congenital muscular dystrophy is a heterogeneous group of inherited muscle diseases characterized clinically by muscle weakness and hypotonia in early infancy. A number of genes harboring causative mutations have been identified, but several cases of congenital muscular dystrophy remain molecularly unresolved. We examined 15 individuals with a congenital muscular dystrophy characterized by early-onset muscle wasting, mental retardation, and peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center on muscle biopsy, and we have identified homozygous or compound heterozygous mutations in the gene encoding choline kinase beta (CHKB). This is the first enzymatic step in a biosynthetic pathway for phosphatidylcholine, the most abundant phospholipid in eukaryotes. In muscle of three affected individuals with nonsense mutations, choline kinase activities were undetectable, and phosphatidylcholine levels were decreased. We identified the human disease caused by disruption of a phospholipid de novo biosynthetic pathway, demonstrating the pivotal role of phosphatidylcholine in muscle and brain.

• 出版日期2011-6-10