Abstract
Remarkable advances have recently elucidated the molecular genetic basis of inherited peripheral neuropathies. These studies revealed a novel mutational mechanism of a large DNA duplication as a cause for a common autosomal dominant demyelinating neuropathy. A peripheral nerve myelin gene, PMP22, located within the duplication is responsible for the demyelinating neuropathy by virtue of a gene dosage effect. The identification of PMP22 and other genes involved in myelinopathies demonstrate that these diseases represent a spectrum of disorders resulting from defects in myelin structure, maintenance, and/or formation.
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Abbreviations
- CMT:
-
Charcot-Marie-Tooth
- CHN:
-
congenital hypomyelinating neuropathy
- CMT1A-REP:
-
24kb repeat sequence
- Cx32:
-
connexin 32 gene
- DSS:
-
Dejerine-Sottas syndrome
- EGR2:
-
early growth response 2 gene
- dup:
-
chromosomal duplication
- FISH:
-
fluorescence in situ hybridization
- HNPP:
-
hereditary neuropathy with liability to pressure palsies
- Mb:
-
megabases
- MPZ:
-
myelin protein zero gene
- NCV:
-
nerve conduction velocity
- P0:
-
myelin protein zero
- PMP22:
-
human peripheral myelin protein gene
- Pmp22:
-
mouse peripheral myelin protein gene
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Acknowledgements
This research would not have been possible without the hard work of postdoctoral fellows, students and technicians in my laboratory, the cooperation and sacrifice of many patients and their families, and the many clinicians caring for neuropathy patients who have shared clinical information and patient samples. Dr. Carlos A. Garcia is greatly appreciated for over a decade of wonderful collaboration. My sincere gratitude to Betty Moseley who has provided years of administrative support. Colleagues in the Department of Molecular and Human Genetics and in the Department of Pediatrics at Baylor College of Medicine have provided an incredibly stimulating environment.
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Lupski, J. Charcot-Marie-Tooth Polyneuropathy: Duplication, Gene Dosage, and Genetic Heterogeneity. Pediatr Res 45, 159–165 (1999). https://doi.org/10.1203/00006450-199902000-00001
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DOI: https://doi.org/10.1203/00006450-199902000-00001
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