Gap junction beta 1 (GJB1) gene mutations in Italian patients with CMT X

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J Hum Genet. 2008 Apr 1

Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-

linked Charcot-Marie-Tooth disease.

Mandich P, Grandis M, Geroldi A, Acquaviva M, Varese A, Gulli R,

Ciotti P, Bellone E.

Department of Neuroscience, Ophthalmology and Genetics, Section of

Medical Genetics, University of Genova, c/o DIMI, Viale Benedetto XV,

6, 16132, Genova, Italy

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.