Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis.

Authors: Mitsuhashi, S  Ohkuma, A  Talim, B  Karahashi, M  Koumura, T  Aoyama, C  Kurihara, M  Quinlivan, R  Sewry, C  Mitsuhashi, H  Goto, K  Koksal, B  Kale, G  Ikeda, K  Taguchi, R  Noguchi, S  Hayashi, YK  Nonaka, I  Sher, RB  Sugimoto, H  Nakagawa, Y  Cox, GA  Topaloglu, H  Nishino, I 
Citation: Mitsuhashi S, etal., Am J Hum Genet. 2011 Jun 10;88(6):845-51.
Pubmed: (View Article at PubMed) PMID:21665002
DOI: Full-text: 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.

Annotation

Disease Annotations
Phenotype Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 6483361
Created: 2012-05-21
Species: All species
Last Modified: 2012-05-21
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.