A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis.
Document Type
Article
Publication Date
2011
Keywords
Child-Preschool, Choline-Kinase, Intellectual-Disability, Mitochondria-Muscle, Muscular-Dystrophies, Mutation, Pedigree, Phosphatidylcholines, Polymorphism-Genetic, Young-Adult
JAX Source
Am J Hum Genet 2011 Jun; 88(6):845-51.
First Page
845
Last Page
851
Abstract
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.
Recommended Citation
Mitsuhashi S,
Ohkuma A,
Talim B,
Ikeda K,
Nonaka I,
Sher RB,
Cox GA,
Topaloglu H,
et a.
A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. Am J Hum Genet 2011 Jun; 88(6):845-51.