title: Mosaicism for the Charcot-Marie-Tooth disease type 1A duplication suggests somatic reversion.
abstract: 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.
authors.affiliation: Institute of Human Genetics, Erlangen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Liehr
authors.forename: B
authors.initials: B
authors.lastname: Rautenstrauss
authors.forename: H
authors.initials: H
authors.lastname: Grehl
authors.forename: K D
authors.initials: KD
authors.lastname: Bathke
authors.forename: A
authors.initials: A
authors.lastname: Ekici
authors.forename: A
authors.initials: A
authors.lastname: Rauch
authors.forename: H D
authors.initials: HD
authors.lastname: Rott
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D009030:Mosaicism / Q000235:genetics*; D010375:Pedigree; D011995:Recombination, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid