Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data.
Clin Genet
; 92(2): 188-198, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28155230
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 ANDMETHODS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitochondrial Encephalomyopathies
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Genetic Predisposition to Disease
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Cytochrome Reductases
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Exome Sequencing
Limits:
Adolescent
/
Adult
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Child
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Female
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Humans
/
Male
Language:
En
Journal:
Clin Genet
Year:
2017
Document type:
Article
Affiliation country:
Country of publication:
DENMARK
/
DINAMARCA
/
DK