Females with CMT1X are usually less severely affected than males. In fact CMT1X clinically manifests in males as early as the first decade of life,

while in females the first CMT symptoms appear only in their third decade; some of them remain entirely asymptomatic for most of their lives. As some women are asymptomatic mutation carriers, a phenotype resembling neuropathy with an X-linked recessive mode of inheritance can be recognized. In line with these clinical observations, EMG studies make it clear that both nerve conduction velocities (NCVs) and compound muscle action Inhibitors,research,lifescience,medical potentials (CMAPs) experience much more limited impairment in CMT1X-affected females than in males (4). At the molecular level, CMT1X disease is caused by mutations in the GJB1 gene coding for the gap-junction AS-703026 mw protein known as connexin 32 (Cx32), Inhibitors,research,lifescience,medical with a molecular weight of 32 kDa (5). Cx32 protein is widely expressed in the myelinating Schwann cells oligomerizing into hemi-channels, forming cell-to-cell gap junctions (6, Inhibitors,research,lifescience,medical 7). The whole family of connexins shares a common membrane topography, with two extra-cellular loops, four trans-membrane segments, and three cytoplasmic domains with carboxy- and

amino-termini (8). In the last 14 years, over 300 mutations in the GJB1 gene have been reported in CMT1X families. These are uniformly distributed throughout the Cx32 gene. However, an X-linked inheritance was not characterized for some GJB1 gene mutations,

because about 30% of them were identified in patients with sporadic disease only (9). The vast majority Inhibitors,research,lifescience,medical of GJB1 gene mutations segregates with a relatively mild phenotype in CMT1X-affected females. We report the results of a study on a five-generation CMT1X family in which it was possible to identify a novel Cys179Gly mutation in the GJB1 gene, located in the highly conservative domain of the Cx32 protein. Patients and Methods Family report The family under study originates Inhibitors,research,lifescience,medical from what was once the Eastern part of Poland, i.e., the city of Lwów (or today’s Ukrainian L’viv). After the Second World War, family members moved to the Western part of modern Poland. The family for which information Nature Reviews Microbiology is available consists of five generations (Fig. ​(Fig.1).1). According to the proband (IV:7) indications, her father (III:3), grandmother (II:2) and great-grandfather (I:1) were all affected by polyneuropathy. Figure 1 Pedigree of five-generation CMTX1 family studied. Arrow indicates proband (IV:7), in whom Cys179Gly mutation in GJB1 gene was first identified. From first to fifth generations, there is no male-to-male transmission, as expected in a typical pattern of … Charcot-Marie-Tooth disease (CMT) was diagnosed in the father (III:3) of the proband, who showed his first CMT symptoms at the age of 13.