Gap junctions (GJs) have emerged as an important molecular component of peripheral myelinated fibers following the discovery of mutations affecting the GJ protein connexin32 (Cx32) in patients with the X-linked Charcot-Marie-Tooth neuropathy (CMT1X).
X-linked Charcot-Marie-Tooth disease (CMT Type X1, OMIM: 302800) represents a frequent cause of hereditary peripheral motor and sensory neuropathies and is associated with mutations in GJB1 encoding the gap junction beta 1 proteinconnexin 32 (Cx32).
In addition to PMP22, GJB1 is the second CMT gene for which both point mutations and genomic rearrangements can cause a neuropathy phenotype, stressing the importance of CMT as a genomic disorder.
Despite confirmation of a connexin 32 point mutation, the patient was treated with 40.5 mg/m(2) of vincristine with no clinical evidence of drug-related neuropathy.
Mice expressing half of the normal dose of protein zero (P0+/- mice) or completely deficient gap-junction protein connexin 32 -/- mice mimic demyelinating forms of inherited neuropathies, such as Charcot-Marie-Tooth (CMT) neuropathies type 1B and CMT type 1X, respectively.
To characterize a large family with X-linked Charcot-Marie-Tooth (CMT) neuropathy without mutations in the gap junction protein B1 (GJB1) gene, which has an unusual phenotype that is different in some aspects from classic CMTX1.
Clinical, electrophysiological and molecular genetic studies in a family with X-linked dominant Charcot-Marie-Tooth neuropathy presenting a novel mutation in GJB1 Promoter and a rare polymorphism in LITAF/SIMPLE.
A Val65Phe amino acid exchange in PMP22 causes CMT type 1 associated with deafness, in GJB1 Tyr7_Thr8delinsSer, Pro172Ala and Ser138Asn are causes of CMTXneuropathies".
These findings propose that a reduced expression of connexin-32 mRNA and protein in the myelin sheath could be responsible for the development of X-linked dominant Charcot-Marie-Tooth neuropathy.
To relate X-linked Charcot-Marie-Tooth disease (CMTX) phenotypes to gender and type of neuropathy by the study of a large series of CMTX patients with proven Cx32 point mutations.