[X-Linked Charcot-Marie-Tooth disease with a new mutation (Thr191Ala) in the connexin32].
We report a 59-year-old man with X-linked Charcot-Marie-Tooth (CMT) disease and a new point mutation in the connexin32 gene. The patient first noticed mild gait disturbance five years previously. On admission, he exhibited muscle atrophy and weakness in the distal part of both legs, mild muscle atrophy of both hands without weakness, and a minimal reduction of touch sensation in the right dorsal foot. Nerve conduction velocity of the peripheral nerves was diffusely reduced. Electromyography exhibited high-amplitude, long-duration, polyphasic motor unit potentials in the muscles of the extremities. Fibrillation potential and positive sharp wave were present in the affected muscles. Cerebrospinal fluid protein was slightly elevated. The polyneuropathy did not respond to high-dose corticosteroid treatment, and showed very slow progression. His parents were not consanguineous. His father and two sons were healthy, but similar illness (more severe) was suspected in his younger brother. Gene analysis (Southern hybridization) did not reveal any duplication or deletion in the CMT 1 A-REP region. However, a novel mutation (Thr191Ala) was detected in the connexin32. Although more than 160 mutations in the connexin 32 gene have been identified worldwide, approximately ten mutations have so far been reported in Japan. In comparison with X-linked CMT patients with other connexin32 mutations, the present case was characterized by late onset and mild neurological manifestation. Gene analysis provides a useful tool for diagnosing cases with slowly progressive, motor dominant polyneuropathy of unknown origin.
Kobari
M
M
Department of Neurology, Tachikawa Hospital.
Irie
J
J
Takizawa
K
K
Yoshihara
T
T
Sobue
G
G
D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D014960:X Chromosome; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D000097002:Gap Junction beta-1 Protein