BACKGROUND: Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) were recently shown to be responsible for autosomal recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal CMT with vocal cord paralysis. METHODS: The coding region of GDAP1 was screened for the presence of mutations in seven families with AR CMT in which the patients were homozygous for markers of the CMT4A locus at chromosome 8q21.1. RESULTS: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon 6 (c.844C>T, R282C). CONCLUSIONS: Mutations in GDAP1 are a frequent cause of AR CMT. They result in an early-onset, severe clinical phenotype. The range of nerve conduction velocities (NCV) is variable. Some patients have normal or near normal NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV compatible with demyelination. The peripheral nerve biopsy findings are equally variable and show features of demyelination and axonal degeneration.
BACKGROUND: Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) were recently shown to be responsible for autosomal recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal CMT with vocal cord paralysis. METHODS: The coding region of GDAP1 was screened for the presence of mutations in seven families with AR CMT in which the patients were homozygous for markers of the CMT4A locus at chromosome 8q21.1. RESULTS: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon 6 (c.844C>T, R282C). CONCLUSIONS: Mutations in GDAP1 are a frequent cause of AR CMT. They result in an early-onset, severe clinical phenotype. The range of nerve conduction velocities (NCV) is variable. Some patients have normal or near normal NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV compatible with demyelination. The peripheral nerve biopsy findings are equally variable and show features of demyelination and axonal degeneration.
Authors: Carly E Siskind; Seema Panchal; Corrine O Smith; Shawna M E Feely; Joline C Dalton; Alice B Schindler; Karen M Krajewski Journal: J Genet Couns Date: 2013-04-21 Impact factor: 2.537
Authors: Magdalena Zimoń; Esra Battaloğlu; Yesim Parman; Sevim Erdem; Jonathan Baets; Els De Vriendt; Derek Atkinson; Leonardo Almeida-Souza; Tine Deconinck; Burcak Ozes; Dirk Goossens; Sebahattin Cirak; Philip Van Damme; Mohammad Shboul; Thomas Voit; Lionel Van Maldergem; Bernard Dan; Mohammed S El-Khateeb; Velina Guergueltcheva; Eduardo Lopez-Laso; Nathalie Goemans; Amira Masri; Stephan Züchner; Vincent Timmerman; Haluk Topaloğlu; Peter De Jonghe; Albena Jordanova Journal: Neurogenetics Date: 2014-09-18 Impact factor: 2.660
Authors: Claudia Gonzaga-Jauregui; Tamar Harel; Tomasz Gambin; Maria Kousi; Laurie B Griffin; Ludmila Francescatto; Burcak Ozes; Ender Karaca; Shalini N Jhangiani; Matthew N Bainbridge; Kim S Lawson; Davut Pehlivan; Yuji Okamoto; Marjorie Withers; Pedro Mancias; Anne Slavotinek; Pamela J Reitnauer; Meryem T Goksungur; Michael Shy; Thomas O Crawford; Michel Koenig; Jason Willer; Brittany N Flores; Igor Pediaditrakis; Onder Us; Wojciech Wiszniewski; Yesim Parman; Anthony Antonellis; Donna M Muzny; Nicholas Katsanis; Esra Battaloglu; Eric Boerwinkle; Richard A Gibbs; James R Lupski Journal: Cell Rep Date: 2015-08-06 Impact factor: 9.423