Back to Search
Start Over
Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange-like phenotype, brain abnormalities and hypertrophic cardiomyopathy
- Source :
- European Journal of Human Genetics, 19, 394-9, European Journal of Human Genetics, 19, 4, pp. 394-9
- Publication Year :
- 2011
-
Abstract
- Contains fulltext : 97138.pdf (Publisher’s version ) (Closed access) 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.
- Subjects :
- Male
Ribosomal Proteins
Cornelia de Lange Syndrome
Nuclear gene
Genomic disorders and inherited multi-system disorders Energy and redox metabolism [IGMD 3]
DNA Copy Number Variations
Mitochondrial translation
Mitochondrion
Biology
medicine.disease_cause
MT-RNR1
Renal disorder Energy and redox metabolism [IGMD 9]
Article
Genomic disorders and inherited multi-system disorders [IGMD 3]
Mitochondrial Proteins
Ribosomal protein
De Lange Syndrome
Genetics
medicine
Humans
Gene
Cells, Cultured
Genetics (clinical)
Mutation
Mitochondrial medicine Energy and redox metabolism [IGMD 8]
Brain
Effective primary care and public health [NCEBP 7]
Cardiomyopathy, Hypertrophic
Microarray Analysis
medicine.disease
Mitochondria
Renal disorder Membrane transport and intracellular motility [IGMD 9]
Mitochondrial medicine [IGMD 8]
Phenotype
Child, Preschool
Microcephaly
Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6]
Subjects
Details
- ISSN :
- 10184813
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics, 19, 394-9, European Journal of Human Genetics, 19, 4, pp. 394-9
- Accession number :
- edsair.doi.dedup.....0fb648a15405d3463aac1cca5fab672a