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Contribution of copy number variations in CMT 1X: a retrospective study
Author(s) -
Capponi S.,
Geroldi A.,
Pezzini I.,
Gulli R.,
Ciotti P.,
Ursino G.,
Lamp M.,
Reni L.,
Sche A.,
Grandis M.,
Mandich P.,
Bellone E.
Publication year - 2015
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12434
Subject(s) - sanger sequencing , copy number variation , breakpoint , multiplex ligation dependent probe amplification , clinical phenotype , gene , medicine , phenotype , genetics , point mutation , pathogenesis , mutation , microbiology and biotechnology , biology , exon , pathology , genome , chromosome
Background and purpose Charcot−Marie−Tooth disease type 1X ( CMT 1X) is an X‐linked dominant hereditary motor‐sensory peripheral neuropathy, which results from mutations in the Gap Junction B1 ( GJB 1 ) gene. In a few cases, gene deletions have been linked to the disease, but their relative contribution in the pathogenesis of CMT 1X has not been assessed yet. Herein a retrospective study to establish the incidence of gene deletions is described. Methods Copy number variation analysis was performed by multiplex ligation‐dependent probe amplification, whilst the breakpoints were defined by Sanger sequencing. Results A novel GJB 1 deletion was identified in a family presenting with a classical CMT 1X phenotype. The rearrangement includes the coding and the regulatory regions of GJB 1 . Conclusions GJB 1 deletions appear to be a rare but not insignificant cause of CMT 1X and are associated with a typical disease phenotype. Accordingly, patients negative for point mutations whose pedigree and clinical records strongly suggest the possibility of CMT 1X should be tested for GJB 1 copy number variations.