title: Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot-Marie-Tooth disease (CMT2K).
abstract: Mutations in GDAP1, an outer mitochondrial membrane protein responsible for recessive Charcot-Marie-Tooth disease (CMT4A), have also been associated with CMT2K, a dominant form of the disease. The three CMT2K patients we studied carried a novel dominant GDAP1 mutation, C240Y (c.719G > A). Mitochondrial respiratory chain complex I activity in fibroblasts from CMT2K patients was 40% lower than in controls, whereas the tubular mitochondria were 33% larger in diameter and the mitochondrial mass was 20% greater. Thus, besides the regulatory role GDAP1 plays in mitochondrial network dynamics, it may also be involved in energy production and in the control of mitochondrial volume.
authors.affiliation: INSERM, U694, 4 rue Larrey, Angers, 49933, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Cassereau
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Naïg
authors.initials: N
authors.lastname: Gueguen
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Malinge
authors.forename: Franck
authors.initials: F
authors.lastname: Letournel
authors.forename: Guillaume
authors.initials: G
authors.lastname: Nicolas
authors.forename: Laurence
authors.initials: L
authors.lastname: Richard
authors.forename: Marc
authors.initials: M
authors.lastname: Ferre
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dubas
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010375:Pedigree
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins; D042967:Electron Transport Complex I