|Title||Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Nambot, S, Gavrilov, D, Thevenon, J, Bruel, AL, Bainbridge, MN, 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|
|Date Published||2017 Feb 02|
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 Journal||Clin. Genet.|