Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 19, Issue 4, Pages 394-399Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2010.214
Keywords
MRPS22; combined OXPHOS deficiency; mitochondrial translation; Cornelia de Lange-like phenotype
Funding
- European Union [LSHMCT-2004-005260]
- Association Francaise contre les Myopathies (AFM)
- Israeli Ministry of Health
Ask authors/readers for more resources
The oxidative phosphorylation (OXPHOS) system is under control of both the mitochondrial and the nuclear genomes; 13 subunits are synthesized by the mitochondrial translation machinery. We report a patient with Cornelia de Lange-like dysmorphic features, brain abnormalities and hypertrophic cardiomyopathy, and studied the genetic defect responsible for the combined OXPHOS complex I, III and IV deficiency observed in fibroblasts. The combination of deficiencies suggested a primary defect associated with the synthesis of mitochondrially encoded OXPHOS subunits. Analysis of mitochondrial protein synthesis revealed a marked impairment in mitochondrial translation. Homozygosity mapping and sequence analysis of candidate genes revealed a homozygous mutation in MRPS22, a gene encoding a mitochondrial ribosomal small subunit protein. The mutation predicts a Leu215Pro substitution at an evolutionary conserved site. Mutations in genes implicated in Cornelia de Lange syndrome or copy number variations were not found. Transfection of patient fibroblasts, in which MRPS22 was undetectable, with the wild-type MRPS22 cDNA restored the amount and activity of OXPHOS complex IV, as well as the 12S rRNA transcript level to normal values. These findings demonstrate the pathogenicity of the MRPS22 mutation and stress the significance of mutations in nuclear genes, including genes that have no counterparts in lower species like bacteria and yeast, for mitochondrial translation defects. European Journal of Human Genetics (2011) 19, 394-399; doi:10.1038/ejhg.2010.214; published online 29 December 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available