%0 Journal Article %J Clin Genet %D 2017 %T Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data. %A Nambot, S %A Gavrilov, D %A Thevenon, J %A Bruel, A L %A Bainbridge, M %A Rio, M %A Goizet, C %A Rötig, A %A Jaeken, J %A Niu, N %A Xia, F %A Vital, A %A Houcinat, N %A Mochel, F %A Kuentz, P %A Lehalle, D %A Duffourd, Y %A Rivière, J B %A Thauvin-Robinet, C %A Beaudet, A L %A Faivre, L %K Adolescent %K Adult %K Child %K Cytochrome Reductases %K Exome Sequencing %K Female %K Genetic Predisposition to Disease %K Heterozygote %K Humans %K Male %K Mitochondrial Encephalomyopathies %K Mutation %K Oxidoreductases Acting on Sulfur Group Donors %K Pedigree %K Young Adult %X

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.

%B Clin Genet %V 92 %P 188-198 %8 2017 Aug %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/28155230?dopt=Abstract %R 10.1111/cge.12985