Is the duplication present in all family members affected with Charcot-Marie-Tooth neuropathy type 1 A?
We studied a family with nine of twenty members affected with Charcot-Marie-Tooth disease type 1A (CMT1A). The proband and her four affected sibs showed no duplication of the 17p11.2-17p12 (CMT region). Two of the proband's affected daughters three affected grandchildren showed duplication of the PMB-22 gene and of the marker VAW409R3 but not of the markers VAW412B3 and EW401. Pulsed field gel electrophoresis (PFGE) revealed a 220 kb SacII fragment in one CMTIA patient with duplication instead of a 500 kb SacII fragment as previously reported. Our findings suggest a smaller size of the duplication in this CMT1A family. The disease segregates with the same haplotype in both duplicated and nonduplicated CMT1A patients. The clinical phenotype showed more severe weakness with earlier onset and motor nerve conduction velocities were characterized by more significant slowing in the patients with duplication than in the patients who did not show duplication.
Department of Pediatrics, University of Iowa, Iowa City 52242.
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Ionăşescu
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Ionăşescu
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Searby
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Barker
D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations / Q000453:epidemiology / Q000235:genetics*; D025063:Chromosome Disorders; D005260:Female; D005819:Genetic Markers; D005821:Genetic Techniques / Q000706:statistics & numerical data; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics
D005819:Genetic Markers