CMT X: GJB1/Connexin 32 whole gene deletions in patients

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Neurogenetics. 2010 Jun 9

GJB1/Connexin 32 whole gene deletions in patients with X-linked

Charcot-Marie-Tooth disease.

Gonzaga-Jauregui C, Zhang F, Towne CF, Batish SD, Lupski JR.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston,

TX, USA.

Abstract

The X-linked form of Charcot-Marie-Tooth disease (CMTX) is the second most

common form of this genetically heterogeneous inherited peripheral neuropathy.

CMT1X is caused by mutations in the GJB1 gene. Most of the mutations causative

for CMT1X are missense mutations.

In addition, a few disease causative nonsense mutations and frameshift deletions

that lead to truncated forms of the protein have also been reported to be

associated with CMT1X. Previously, there have been reports of patients with

deletions of the coding sequence of GJB1; however, the size and breakpoints of

these deletions were not assessed.

Here, we report five patients with deletions that range in size from 12.2 to

48.3 kb and that completely eliminate the entire coding sequence of the GJB1

gene, resulting in a null allele for this locus. Analyses of the breakpoints of

these deletions showed that they are nonrecurrent and that they can be generated

by different mechanisms. In addition to PMP22, GJB1 is the second CMT gene for

which both point mutations and genomic rearrangements can cause a neuropathy

phenotype, stressing the importance of CMT as a genomic disorder.