Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data

Clin Genet. 2017 Aug;92(2):188-198. doi: 10.1111/cge.12985. Epub 2017 Mar 1.


Background: Alterations in GFER gene have been associated with progressive mitochondrial myopathy, congenital cataracts, hearing loss, developmental delay, lactic acidosis and respiratory chain deficiency in 3 siblings born to consanguineous Moroccan parents by homozygosity mapping and candidate gene approach (OMIM#613076). Next generation sequencing recently confirmed this association by the finding of compound heterozygous variants in 19-year-old girl with a strikingly similar phenotype, but this ultra-rare entity remains however unknown from most of the scientific community.

Materials and methods: Whole exome sequencing was performed as part of a "diagnostic odyssey" for suspected mitochondrial condition in 2 patients, presenting congenital cataracts, progressive encephalomyopathy and hypotrophy and detected unreported compound heterozygous variants in GFER.

Results: Thanks to an international data sharing, we found 2 additional patients carrying compound heterozygous variants in GFER. Reverse phenotyping confirmed the phenotypical similarities between the 4 patients. Together with the first literature reports, the review of these 8 cases from 4 unrelated families enables us to better describe this apparently homogeneous disorder, with the clinical and biological stigmata of mitochondrial disease.

Conclusion: This report highlights the clinical utility of whole exome sequencing and reverse phenotyping for the diagnosis of ultra-rare diseases and underlines the importance of a broad data sharing for accurate clinical delineation of previously unrecognized entities.

Keywords: GFER; data sharing; mitochondrial condition; whole-exome sequencing.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cytochrome Reductases / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Humans
  • Male
  • Mitochondrial Encephalomyopathies / genetics*
  • Mitochondrial Encephalomyopathies / physiopathology
  • Mutation
  • Pedigree
  • Whole Exome Sequencing*
  • Young Adult


  • Cytochrome Reductases
  • GFER protein, human