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Clin Genet. 2017 Aug;92(2):188-198. doi: 10.1111/cge.12985. Epub 2017 Mar 1.

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

Author information

1
Centre de Génétique et Centre de référence «Anomalies du Développement et Syndromes Malformatifs», Hôpital d'Enfants, Centre Hospitalier Universitaire de Dijon, Dijon, France.
2
Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, Centre Hospitalier Universitaire de Dijon, Dijon, France.
3
Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
4
Department of Genetics and Genomics, Mayo Clinic College of Medicine, Rochester, Minnesota.
5
Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), Centre Hospitalier Universitaire de Dijon et Université de Bourgogne-Franche Comté, Dijon, France.
6
Génétique des Anomalies du Développement, Université de Bourgogne, Dijon, France.
7
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
8
Service de Génétique Médicale, Hôpital Necker Enfants Malades, Paris, France.
9
Service de Génétique Médicale, Centre Hospitalier Universitaire de Bordeaux-GH Pellegrin, Bordeaux, France.
10
Laboratoire de Génétique Moléculaire, Institut de Recherche Necker Enfants Malades, Hôpital Necker Enfants Malades, Paris, France.
11
Center for Metabolic Diseases, University Hospital Gasthuisberg, Leuven, Belgium.
12
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
13
Service de Pathologie, Pôle Biologie et Pathologie, Centre Hospitalier Universitaire de Bordeaux-GH Pellegrin, Bordeaux, France.
14
Service de Génétique médicale, Centre Hospitalier Universitaire La Pitié Salpêtrière-Charles Foix, Paris, France.

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.

KEYWORDS:

GFER ; data sharing; mitochondrial condition; whole-exome sequencing

PMID:
28155230
DOI:
10.1111/cge.12985
[Indexed for MEDLINE]

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