Mapping of Charcot-Marie-Tooth disease type 1C to chromosome 16p identifies a novel locus for demyelinating neuropathies.
Charcot-Marie-Tooth (CMT) neuropathy represents a genetically heterogeneous group of diseases affecting the peripheral nervous system. We report genetic mapping of the disease to chromosome 16p13.1-p12.3, in two families with autosomal dominant CMT type 1C (CMT1C). Affected individuals in these families manifest characteristic CMT symptoms, including high-arched feet, distal muscle weakness and atrophy, depressed deep-tendon reflexes, sensory impairment, slow nerve conduction velocities, and nerve demyelination. A maximal combined LOD score of 14.25 was obtained with marker D16S500. The combined haplotype analysis in these two families localizes the CMT1C gene within a 9-cM interval flanked by markers D16S519 and D16S764. The disease-linked haplotypes in these two pedigrees are not conserved, suggesting that the gene mutation underlying the disease in each family arose independently. The epithelial membrane protein 2 gene (EMP2), which maps to chromosome 16p13.2, was evaluated as a candidate gene for CMT1C.
Street
Valerie A
VA
V. M. Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, WA 98195, USA.
Goldy
Jeff D
JD
Golden
Alana S
AS
Tempel
Bruce L
BL
Bird
Thomas D
TD
Chance
Phillip F
PF
D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003711:Demyelinating Diseases / Q000145:classification / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008126:Lod Score; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D010375:Pedigree; D011995:Recombination, Genetic / Q000235:genetics
C486403:EMP2 protein, human; D005819:Genetic Markers; D008562:Membrane Glycoproteins