Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data. Issue 2 (1st March 2017)

• Record Type: Journal Article
• Authors: Nambot, S.; Gavrilov, D.; Thevenon, J.; Bruel, A.L.; 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, J.B.; Thauvin‐Robinet, C.; Beaudet, A.L.; Faivre, L.
• Is Part Of: Clinical genetics. Volume 92:Issue 2(2017)
• Page Start: 188
• Page End: 198
• Publication Date: 2017-03-01
• Subjects: data sharing -- GFER -- mitochondrial condition -- whole‐exome sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12985
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract : 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. Abstract :