Moszyńka I, Kabzińska D, Kochański A
Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
Acta Myol. 2009 Oct;28(2):72-5.
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.
夏科-马里-图思病1X型（CMT1X）以X连锁显性性状遗传。女性CMT1X患者通常症状较轻，甚至是编码缝隙连接蛋白连接蛋白-32（Cx32）的GJB1基因突变的无症状携带者。在本报告中，描述了一个五代CMT1X家族，从中鉴定出GJB1基因中的新突变Cys179Gly。Cys179Gly突变位于Cx32蛋白的高度保守结构域。先前在卵母细胞系统中进行的功能研究表明，高度保守的Cx32半胱氨酸残基中的点突变会导致缝隙连接功能完全丧失。然而，尽管存在严重的生化缺陷，Cys179Gly突变却与轻度CMT1X表型共分离。这项研究进一步证明了GJB1突变的生化效应与CMT1X表型之间的差异。
