Mosaicism for the Charcot-Marie-Tooth disease type 1A duplication suggests somatic reversion

A female patient with clinical signs and symptoms of a demyelinating neuropathy was shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2, typical of the great majority of cases of Charcot-Marie-Tooth disease type 1A (CMT1A). However, analysis of DNA extracted from peripheral blood...

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Bibliographic Details
Published inHuman genetics Vol. 98; no. 1; p. 22
Main Authors Liehr, T, Rautenstrauss, B, Grehl, H, Bathke, K D, Ekici, A, Rauch, A, Rott, H D
Format Journal Article
LanguageEnglish
Published Germany 01.07.1996
Subjects
Adult
Blotting, Southern
Charcot-Marie-Tooth Disease - genetics
Chromosome Aberrations
Chromosomes, Human, Pair 17 - genetics
Crossing Over, Genetic - genetics
Female
Humans
In Situ Hybridization, Fluorescence
Interphase
Mosaicism - genetics
Pedigree
Recombination, Genetic - genetics
Repetitive Sequences, Nucleic Acid
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Summary:A female patient with clinical signs and symptoms of a demyelinating neuropathy was shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2, typical of the great majority of cases of Charcot-Marie-Tooth disease type 1A (CMT1A). However, analysis of DNA extracted from peripheral blood revealed a 2:2.4 instead of the usual 2:3 ratio between the 7.8- and 6.0-kb EcoRI fragments in the proximal and distal repetitive extragenic palindromic (REP) elements of CMT1A. Detection of a 3.2-kb EcoRI/SacI kb junction fragment with probe pLR7.8 confirmed the CMT1A duplication. The dosage of this junction fragment, compared with a 2.8-kb EcoRI/SacI fragment of the proximal REP elements of CMT1A, was 2:0.58 instead of the expected 2:1 dosage for heterozygous CMT1A duplications. We hypothesized that the lower dosages of these restriction fragments specific for the CMT1A duplication were due to mosaicism; this was confirmed by fluorescence in situ hybridization analysis with the D17S122-specific probe pVAW409R1. In peripheral blood lymphocytes the percentage of interphase nuclei with a duplication in 17p11.2 was 49%. In interphase nuclei extracted from buccal mucosa, hair-root cells or paraffin-embedded nervous tissue the duplication was detectable in 51%, 66% and 74%, respectively. This is the first report of mosaicism in a patient with a CMT1A duplication identified by three different and independent techniques.
ISSN:0340-6717
DOI:10.1007/s004390050154