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Clinical and pathological observations in men lacking the gap junction protein connexin 32
Author(s) -
Hahn Angelika F.,
Ainsworth Peter J.,
Naus Christian C. G.,
Mao Jian,
Bolton Charles F.
Publication year - 2000
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/1097-4598(2000)999:9<::aid-mus8>3.0.co;2-c
Subject(s) - connexin , missense mutation , biology , gap junction , nonsense mutation , mutation , schwann cell , connexin 32 , phenotype , pathological , sural nerve , loss function , genetics , axon , pathology , gene , microbiology and biotechnology , anatomy , medicine , intracellular
The X‐linked form of Charcot–Marie–Tooth disease has been associated with mutations in the connexin 32 ( Cx 32 ) gene , which encodes a gap junction protein. The majority of identified mutations are missense, but a few nonsense mutations or frame‐shifting microdeletions have been encountered. Functional assessments of the mutated gap junction protein have demonstrated altered or simple losses of function. Mutations segregate with a typical clinical phenotype, which is the result of an age‐related, progressive neuropathy. The mechanisms that cause the nerve damage are unknown. This report describes the consequences of a unique deletion mutation that eliminates the entire coding sequence of Cx 32, resulting in the absence of the Cx 32 gap junction protein in affected, hemizygous men. The clinical expression of this unique mutation was studied by the clinical, electrophysiological, and pathological evaluation of this kinship of five generations. The resulting severe neuropathy combines features of demyelination, notably in paranodal distribution, and distal accentuated axonal degeneration. The predicted absence of Cx 32 gap junctions is shown to be associated with a severe dysfunction of the axon–Schwann cell unit. Observed changes resemble those of Cx 32 ‐null mice. No central nervous system changes were demonstrated. © 2000 John Wiley & Sons, Inc. Muscle Nerve Supplement 9:S39–S48, 2000.