Journal article
T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy
Annals of neurology, Vol.59(2), pp.358-364
2006
DOI: 10.1002/ana.20777
PMID: 16437560
Abstract
Objective: To determine the clinical consequences of the PMP22 point mutation, T118M, which has been previously considered to either cause an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism.
Methods: We analyzed patients from five separate kindreds and characterized their peripheral nerve function by clinical and electrophysiological methods.
Results: All heterozygous patients had clinical and/or electrophysiological features of a neuropathy similar to hereditary neuropathy with liability to pressure palsies (HNPPs). The homozygous patient had a severe axonal neuropathy without features of demyelination.
Interpretation: These findings suggest that T118M PMP22 retains some normal PMP22 activity, allowing the formation of compact myelin and normal nerve conduction velocities in the homozygous state. Taken together, these findings suggest that T118M is a pathogenic mutation causing a dominantly inherited form of CMT by a partial loss of PMP22 function.
Details
- Title: Subtitle
- T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy
- Creators
- Michael E SHY - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United StatesMena T SCAVINA - Department of Neurology, DuPont Hospital for Children, Wilmington, DE, United StatesSteven S SCHERER - Department of Neurology, University of Pennsylvania, Philadelphia, PA, United StatesJames R LUPSKI - Department of Molecular and Human Genet ics, Baylor College of Medicine, Houston, TX, United StatesAlisa CLARK - Department of Neurology, DuPont Hospital for Children, Wilmington, DE, United StatesKaren M KRAJEWSKI - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United StatesJun Li - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United StatesJohn KAMHOLZ - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United StatesEdwin KOLODNY - Division of Neurogenetics, NYU School of Medicine, New York, NY, United StatesKinga SZIGETI - Department of Molecular and Human Genet ics, Baylor College of Medicine, Houston, TX, United StatesRichard A FISCHER - Department of Neurology, DuPont Hospital for Children, Wilmington, DE, United StatesGulam Mustafa SAIFI - Department of Molecular and Human Genet ics, Baylor College of Medicine, Houston, TX, United States
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.59(2), pp.358-364
- Publisher
- Willey-Liss; Hoboken
- DOI
- 10.1002/ana.20777
- PMID
- 16437560
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Grant note
- DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke; name: NIH, award: R01NS27042, R01NS43560, K08 NS048204; DOI: 10.13039/100005202, name: Muscular Dystrophy Association
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984014016902771
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