Abstract:CMT1X, an X-linked inherited neuropathy, is caused by mutations in GJB1, which codes for Cx32, a gap junction protein expressed by Schwann cells and oligodendrocytes. Many GJB1 mutations cause central nervous system (CNS) abnormality in males, including stable subclinical signs and, less often, short-duration episodes characterized by motor difficulties and altered consciousness. However, some mutations have no apparent CNS effects. What distinguishes mutations with and without CNS manifestations has been uncl… Show more
“…This p.Trp132* variant has previously been reported in a Japanese male patient but no CNS involvement was documented . In recent research the GJB1 mutations were grouped into ‘peripheral nervous system only’ and mutations with CNS manifestations, and a distinct expression of gap junction plaques was revealed . But our findings argue that other underlying genetic or epigenetic factors might also contribute to the clinical diversity of CMTX1.…”
A relatively lower frequency of CMTX1 (5.9%) was demonstrated and a broad mutation spectrum of GJB1 was described. Detailed clinical differences between genders and various central nervous system symptoms were also illustrated, even in the same pedigree.
“…This p.Trp132* variant has previously been reported in a Japanese male patient but no CNS involvement was documented . In recent research the GJB1 mutations were grouped into ‘peripheral nervous system only’ and mutations with CNS manifestations, and a distinct expression of gap junction plaques was revealed . But our findings argue that other underlying genetic or epigenetic factors might also contribute to the clinical diversity of CMTX1.…”
A relatively lower frequency of CMTX1 (5.9%) was demonstrated and a broad mutation spectrum of GJB1 was described. Detailed clinical differences between genders and various central nervous system symptoms were also illustrated, even in the same pedigree.
“…Nevertheless, other studies have recently observed that even mutations associated with a complete loss of Cx32 can produce CNS dysfunction 41. Although a specific genotype-phenotype correlation between Cx32 mutation location (extracellular, intracellular or transmembrane) and WMLs has not been observed, recent studies suggest that the ability of Cx32 mutants to form gap junction plaques and produce adequate levels of junctional coupling in oligodendrocytes may relate to CNS manifestations 42. To all of the above, the occasional triggering of immune-mediated demyelination is also speculated to contribute to WMLs, as previously discussed 30…”
We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for mutations acting as a possible MS risk factor.
“…Interesting, polymorphism in GJB1 are extremely rare, and a Although many other abnormalities in addition to peripheral neuropathy may be found in CMT, including central nervous system abnormalities, 14 spinal deformities, 15 and sensorineural deafness, [16][17][18] none of the patients included in this study had any of these manifestations. One patient (1.II-3) had neuropathic pain.…”
Section: Iii-2) Were Within Normal Values (Tables 1 and 2) It Is Verymentioning
Mutations in the GJB1 gene are the second most frequent cause of Charcot‐Marie‐Tooth disease (CMT), accounting for approximately 10% of CMT cases worldwide. We retrospectively analyzed detailed clinical and neurophysiological data on four Brazilian families carrying novel mutations of the GJB1 gene. Mutations were identified by bidirectional Sanger sequence analysis on the GJB1 coding region. We identified a total of 12 subjects from four different kindred. There was no male‐to‐male transmission, and their clinical pictures were within the expected spectrum for GJB1‐related neuropathy. Males were more severely affected than females. Five out of the eight females only had subclinical neuropathy. Nerve conduction velocities were in the intermediate range in the male patients and higher in the females affected. These mutations increase the genotypic variability associated with GJB1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.