Mild form of CMT 1X disease caused by a novel Cys179Gly mutation in the GJB1/Cx

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Acta Myol. 2009 Oct;28(2):72-5.

Mild form of Charcot-Marie-Tooth type 1X disease caused by a novel Cys179Gly

mutation in the GJB1/Cx32 gene.

Moszyñka I, Kabziñska D, Kochañski A.

Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of

Sciences, Warszawa, Poland.

Charcot-Marie-Tooth type 1X (CMT1X) disease is inherited as an X-linked dominant

trait. Female CMT1X patients are usually mildly affected or even asymptomatic

carriers of mutations in the GJB1 gene coding for a gap junction protein called

connexin-32 (Cx32).

In this report, a five-generation CMT1X family is described from which the new

mutation in the GJB1 gene Cys179Gly was identified. The Cys179Gly mutation is

located in the highly conservative domain of the Cx32 protein. Previous

functional studies performed in the oocyte system have shown that point

mutations in the highly conserved Cx32 cysteine residues result in a complete

loss of function of the gap junction. However, despite severe biochemical

defects, the Cys179Gly mutation segregates with a mild CMT1X phenotype.

This study further documents a discrepancy between biochemical effects of GJB1

mutations and the CMT1X phenotype.