title: Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-linked Charcot-Marie-Tooth disease.
abstract: X-linked Charcot-Marie-Tooth disease (CMT1X) is a peripheral neuropathy transmitted in a dominant manner and caused by mutations in the Connexin 32 (Cx32) gene (GJB1, gap junction beta 1). Here we report the mutation analysis of the GJB1 gene in 76 subjects with possible CMT1 and absence of 17p11.2 duplication, and in 38 CMT2 patients without mutations in CMT2-associated-genes, selected from a cohort of 684 patients with peripheral sensory-motor neuropathy. The analysis was performed by direct sequencing of the coding sequence and exon/intron boundaries of the GJB1 gene. The mutation screening identified 22 mutations in GJB1, eight of which have not been previously published: six point mutations (c.50C > G, c.107T > A, c.545C > T, c.545C > G, c.548G > C, c.791G > T) and two deletions (c.84delC, c.573_581delCGTCTTCAT). The GJB1 mutation frequency (19.3%) and the clinical heterogeneity of our patients suggest searching for GJB1 mutations in all CMT cases without the 17p11.2 duplication, regardless of the gender of the proband, as well as in CMT2 patients with possible X-linked inheritance.
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy. pmandich@unige.it.
authors: Paola
authors: P
authors: Mandich
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Neurology and Neurological Rehabilitation, University of Genova, Genova, Italy.
authors: Marina
authors: M
authors: Grandis
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy.
authors: Alessandro
authors: A
authors: Geroldi
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy.
authors: Massimo
authors: M
authors: Acquaviva
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy.
authors: Alessandra
authors: A
authors: Varese
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy.
authors: Rossella
authors: R
authors: Gulli
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy.
authors: Paola
authors: P
authors: Ciotti
authors: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV, 6, 16132, Genova, Italy.
authors: Emilia
authors: E
authors: Bellone
mesh_terms: D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D017354:Point Mutation; D017384:Sequence Deletion; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D004247:DNA; D000097002:Gap Junction beta-1 Protein