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

TitleFurther delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data.
Publication TypeJournal Article
Year of Publication2017
AuthorsNambot, S, Gavrilov, D, Thevenon, J, Bruel, AL, Bainbridge, M, Rio, M, Goizet, C, Rötig, A, Jaeken, J, Niu, N, Xia, F, Vital, A, Houcinat, N, Mochel, F, Kuentz, P, Lehalle, D, Duffourd, Y, Rivière, JB, Thauvin-Robinet, C, Beaudet, AL, Faivre, L
JournalClin Genet
Date Published2017 Aug
KeywordsAdolescent, Adult, Child, Cytochrome Reductases, Exome Sequencing, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Mitochondrial Encephalomyopathies, Mutation, Oxidoreductases Acting on Sulfur Group Donors, Pedigree, Young Adult

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.

Alternate JournalClin Genet
PubMed ID28155230

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