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

S. Nambot, D. Gavrilov, J. Thevenon, A.L. Bruel, M. Bainbridge, M. Rio, C. Goizet, A. Rötig, J. Jaeken, N. Niu, F. Xia, A. Vital, N. Houcinat, F. Mochel, P. Kuentz, D. Lehalle, Y. Duffourd, J.B. Rivière, C. Thauvin-Robinet, A.L. Beaudet, L. Faivre
Clin Genet. 2017-03-01; 92(2): 188-198
DOI: 10.1111/cge.12985

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1. 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.

Nambot S(1)(2), Gavrilov D(3)(4), Thevenon J(1)(5)(6), Bruel AL(2)(6), Bainbridge
M(7), Rio M(8), Goizet C(9), Rötig A(10), Jaeken J(11), Niu N(12), Xia F(12),
Vital A(13), Houcinat N(1), Mochel F(14), Kuentz P(2), Lehalle D(1), Duffourd
Y(5)(6), Rivière JB(2)(5)(6), Thauvin-Robinet C(1)(5)(6), Beaudet AL(12), Faivre
L(1)(5)(6).

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.

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.

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Auteurs Bordeaux Neurocampus