1. A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K
- Author
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Arnaud Chevrollier, Marc Ferré, Dominique Bonneau, Vincent Procaccio, Julien Cassereau, Pascal Reynier, Christophe Verny, BMC, Ed., Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), and Département de Biochimie et Génétique [Angers]
- Subjects
Male ,inherited peripheral neuropathy ,Human Variome Project ,lcsh:Medicine ,Locus (genetics) ,Genes, Recessive ,Nerve Tissue Proteins ,Disease ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Biology ,computer.software_genre ,03 medical and health sciences ,0302 clinical medicine ,Charcot-Marie-Tooth Disease ,Databases, Genetic ,Humans ,Genetics(clinical) ,Pharmacology (medical) ,Genetic Predisposition to Disease ,ganglioside-induced differentiation-associated protein 1 (GDAP1) ,Mobility Limitation ,Gene ,Genetics (clinical) ,Genetic Association Studies ,030304 developmental biology ,Genes, Dominant ,Genetics ,Medicine(all) ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Database ,Research ,ganglioside-induced differentiation- associated protein 1 (GDAP1) ,lcsh:R ,Inherited Peripheral Neuropathy ,General Medicine ,Phenotype ,Human genetics ,Electrophysiology ,Charcot-Marie-Tooth disease (CMT) ,Wheelchairs ,Mutation ,Female ,Bacterial outer membrane ,computer ,locus-specific database (LSDB) ,030217 neurology & neurosurgery - Abstract
Background The ganglioside-induced differentiation-associated protein 1 gene (GDAP1), which is involved in the Charcot-Marie-Tooth disease (CMT), the most commonly inherited peripheral neuropathy, encodes a protein anchored to the mitochondrial outer membrane. The phenotypic presentations of patients carrying GDAP1 mutations are heterogeneous, making it difficult to determine genotype-phenotype correlations, since the majority of the mutations have been found in only a few unrelated patients. Locus-specific databases (LSDB) established in the framework of the Human Variome Project provide powerful tools for the investigation of such rare diseases. Methods and Results We report the development of a publicly accessible LSDB for the GDAP1 gene. The GDAP1 LSDB has adopted the Leiden Open-source Variation Database (LOVD) software platform. This database, which now contains 57 unique variants reported in 179 cases of CMT, offers a detailed description of the molecular, clinical and electrophysiological data of the patients. The usefulness of the GDAP1 database is illustrated by the finding that GDAP1 mutations lead to primary axonal damage in CMT, with secondary demyelination in the more severe cases of the disease. Conclusion Findings of this nature should lead to a better understanding of the pathophysiology of CMT. Finally, the GDAP1 LSDB, which is part of the mitodyn.org portal of databases of genes incriminated in disorders involving mitochondrial dynamics and bioenergetics, should yield new insights into mitochondrial diseases.
- Published
- 2011