Exome sequencing identifies MRPL3 mutation in mitochondrial cardiomyopathy

Hum Mutat. 2011 Nov;32(11):1225-31. doi: 10.1002/humu.21562. Epub 2011 Sep 14.


By combining exome sequencing in conjunction with genetic mapping, we have identified the first mutation in large mitochondrial ribosomal protein MRPL3 in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency. Affected sibs were compound heterozygotes for a missense MRPL3 mutation (P317R) and a large-scale deletion, inherited from the mother and the father, respectively. These mutations were shown to alter ribosome assembly and cause a mitochondrial translation deficiency in cultured skin fibroblasts resulting in an abnormal assembly of several complexes of the respiratory chain. This observation gives support to the view that exome sequencing combined with genetic mapping is a powerful approach for the identification of new genes of mitochondrial disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology
  • DNA Mutational Analysis
  • DNA, Mitochondrial / chemistry
  • Exome
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Sequence Deletion


  • DNA, Mitochondrial
  • MRPL3 protein, human
  • Mitochondrial Proteins
  • Ribosomal Proteins