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. 2001 Oct;69(4):883-8.
doi: 10.1086/323743. Epub 2001 Aug 28.

Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12-p13.2

M L Kennerson  1 , D Zhu, R J Gardner, E Storey, J Merory, S P Robertson, G A Nicholson
Affiliations

Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12-p13.2

M L Kennerson et al. Am J Hum Genet. 2001 Oct.

Abstract

The hereditary disorders of peripheral nerve form one of the most common groups of human genetic diseases, collectively called Charcot-Marie-Tooth (CMT) neuropathy. Using linkage analysis we have identified a new locus for a form of CMT that we have called "dominant intermediate CMT" (DI-CMT). A genomewide screen using 383 microsatellite markers showed strong linkage to the short arm of chromosome 19 (maximum LOD score 4.3, with a recombination fraction (straight theta) of 0, at D19S221 and maximum LOD score 5.28, straight theta=0, at D19S226). Haplotype analysis performed with 14 additional markers placed the DI-CMT locus within a 16.8-cM region flanked by the markers D19S586 and D19S546. Multipoint linkage analysis suggested the most likely location at D19S226 (maximum multipoint LOD score 6.77), within a 10-cM confidence interval. This study establishes the presence of a locus for DI-CMT on chromosome 19p12-p13.2.

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Figures

Figure 1
Figure 1
Genetic map (sex averaged) of chromosome 19 markers used in this study. The genetic distances were obtained from the Marshfield map. Loci that appear on the same line map to the same genetic location. The order of these markers was obtained from the chromosome 19 p-arm metric physical map. Markers defining the DI-CMT genetic interval are shown in boldface.
Figure 2
Figure 2
Haplotype analysis of markers from chromosome 19p12-p13.2 in family (DI-CMT310) with autosomal dominant intermediate CMT. The haplotype segregating with the disease is boxed. The markers are presented in order from telomere (top) to centromere (bottom). Blackened symbols denote affected individuals, and unblackened symbols denote unaffected individuals. Individuals are numbered consecutively in each generation, from left to right. Individuals IV-1 and IV-12 define the centromeric boundary of the disease at D19S546, whereas individual IV-16 defines the telomeric boundary at D19S586.
Figure 3
Figure 3
Multipoint localization of dominant intermediate CMT. Genetic location (distance, in cM, from the telomere of chromosome 19p) is plotted against the multipoint LOD score. Markers used in the multipoint analysis are shown. A maximum multipoint LOD score of 6.77 was obtained for D19S226 at 42.28 cM. The markers D19S586 and D19S199 flank the 10-cM confidence interval.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics/Map_Markers/maps/IndexMapF...
    1. Chromosome 19 p Arm Metric Physical Map, Lawrence Livermore Laboratory, http://greengenes.llnl.gov/genome-bin/loadmap?region=mp
    1. GenBank, http://www.ncbi.nlm.nih.gov/ (for PMP22 [accession number L03203], Cx32/GJB1 [accession number XM_047682], MPZ/Po [accession number D10537 D90501], EGR2 [accession number AF139463], MTMR2 [accession number NM_003912], NDRG1 [accession number XM_051273], NTRK1/TrkA [accession number XM_043533], PRX [accession number XM_047407], NEFL [accession number X05608], KIF1Bβ [accession number AB023656])
    1. Genome Database, http://www.gdb.org/
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for CMT1A [MIM 118220], CMT1B [MIM 118200], CMT1X [MIM 302800], CMT2A [MIM 118210], CMT2B [ MIM 600882], CMT2C [MIM 606071], CMT2D [MIM 601472], and CMT2E [162280])

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