Mild form of Charcot-Marie-Tooth type 1X disease caused by a novel Cys179Gly mutation in the GJB1/Cx32 gene.
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.
Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
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I
Moszyńka
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D
Kabzińska
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Kochański
D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D017421:Sequence Analysis; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D000097002:Gap Junction beta-1 Protein