Hereditary motor and sensory neuropathy (HMSN) type X1 in an Argentinean family reveals independent GJB1/Cx32 mutations at the identical nucleotide position.

Abstract	X-linked Charcot-Marie-Tooth disease (CMT Type X1, OMIM: 302800) represents a frequent cause of hereditary peripheral motor and sensory neuropathies and is associated with mutations in GJB1 encoding the gap junction beta 1 protein connexin 32 (Cx32). Studying an Argentinean family of Italian origin with seven affected males in three generations exhibiting clinical signs of CMT, eight obligate female carriers were identified genealogically. DNA sequencing of exon 2 and adjacent regions of the GJB1 gene in two symptomatic males whose respective maternal grandfathers, both affected, were brothers, revealed mutations in GJB1/Cx32. Surprisingly, each of the two affected patients had a different mutation in hemizygous state at the same nucleotide position: c.383C>T (p.S128L) and c.383C>A (p.S128X). In both cases, the identified mutation was present in heterozygous state in the corresponding maternal genomic DNA. Furthermore, X-chromosomal microsatellite analysis showed identical marker alleles in both patients. Together with the genealogical information, these molecular data imply that a primarily mutated allele mutated for a second time. In conclusion, two different mutations at the same nucleotide position in this Argentinean family represent a finding with a very low probability of occurrence.
Authors	Wanda Maria Gerding, Judith Koetting, Lucía Paola Rey, Hilda Bibas Bonet, Mirta Esther Abdala, Anna Mazzeo, Maria Luisa Mostacciuolo, Larissa Arning, Roque Carrero-Valenzuela
Journal	Molecular and cellular probes (Mol Cell Probes) 2013 Jun-Aug Vol. 27 Issue 3-4 Pg. 118-21 ISSN: 1096-1194 [Electronic] England
PMID	23384994 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2013 Elsevier Ltd. All rights reserved.
Chemical References	Connexins connexin 32
Topics	Alleles Argentina Charcot-Marie-Tooth Disease (ethnology, genetics) Connexins (genetics) Female Haplotypes Humans Male Microsatellite Repeats Mutation Pedigree Phenotype Polymorphism, Single Nucleotide

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