Journal article
Charcot-Marie-Tooth disease and related neuropathies: Mutation distribution and genotype-phenotype correlation
Annals of neurology, Vol.51(2), pp.190-201
2002
DOI: 10.1002/ana.10089
PMID: 11835375
Abstract
Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disorder that has been associated with alterations of several proteins: peripheral myelin protein 22, myelin protein zero, connexin 32, early growth response factor 2, periaxin, myotubularin related protein 2, N-myc downstream regulated gene 1 product, neurofilament light chain, and kinesin 1B. To determine the frequency of mutations in these genes among patients with CMT or a related peripheral neuropathy, we identified 153 unrelated patients who enrolled prior to the availability of clinical testing, 79 had a 17p12 duplication (CMT1A duplication), 11 a connexin 32 mutation, 5 a myelin protein zero mutation, 5 a peripheral myelin protein 22 mutation, 1 an early growth response factor 2 mutation, 1 a periaxin mutation, 0 a myotubularin related protein 2 mutation, 1 a neurofilament light chain mutation, and 50 had no identifiable mutation; the N-myc downstream regulated gene 1 and the kinesin 1B gene were not screened for mutations. In the process of screening the above cohort of patients as well as other patients for CMT-causative mutations, we identified several previously unreported mutant alleles: two for connexin 32, three for myelin protein zero, and two for peripheral myelin protein 22. The peripheral myelin protein 22 mutation W28R was associated with CMT1 and profound deafness. One patient with a CMT2 clinical phenotype had three myelin protein zero mutations (I89N+V92M+I162M). Because one-third of the mutations we report arose de novo and thereby caused chronic sporadic neuropathy, we conclude that molecular diagnosis is a necessary adjunct for clinical diagnosis and management of inherited and sporadic neuropathy.
Details
- Title: Subtitle
- Charcot-Marie-Tooth disease and related neuropathies: Mutation distribution and genotype-phenotype correlation
- Creators
- Cornelius F BOERKOEL - Department of Molecularand Human Genetics, Baylor College of Medicine, Houston, TX, United StatesHiroshi TAKASHIMA - Department of Molecularand Human Genetics, Baylor College of Medicine, Houston, TX, United StatesLowell L WILLIAMS - Department of Molecularand Human Genetics, Baylor College of Medicine, Houston, TX, United StatesPedro MANCIAS - Department of Neurology, University of Texas-Houston Health Science Center Medical School, Houston, TX, United StatesLan J BUTLER - Department of Neurology, University of Texas-Houston Health Science Center Medical School, Houston, TX, United StatesKaren KRAJEWSKI - Department of Neurology. Wayne State University, Detroit, MI, United StatesMichael SHY - Department of Neurology. Wayne State University, Detroit, MI, United StatesJames R LUPSKI - Department of Molecularand Human Genetics, Baylor College of Medicine, Houston, TX, United StatesCarlos A GARCIA - Departments of Neurology and Pathology, Tulane University Health Sciences Center, New Orleans, LA, United StatesRichard K OLNEY - Department of Neurology, University of California San Francisco School of Medicine, San Francisco, CA, United StatesJohn JOHNSON - Clinical Genetics, Shodair Children's Hospital, Helena, MT, United StatesKatherine BERRY - Clinical Genetics, Shodair Children's Hospital, Helena, MT, United StatesPaul RUSSO - Kaukauna Clinic, Kaukauna, WI, United StatesShelley KENNEDY - Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, CanadaAhmad S TEEBI - Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, CanadaMena SCAVINA - Division of Neurology, duPont Hospital for Children, Wilmington, DE, United States
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.51(2), pp.190-201
- Publisher
- Willey-Liss; Hoboken
- DOI
- 10.1002/ana.10089
- PMID
- 11835375
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Language
- English
- Date published
- 2002
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020743002771
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