New Mutation Type X - from Japan

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(New Mutation in CMT Type X)

1: Rinsho Shinkeigaku 2000 Sep;40(9):896-9

[X-Linked Charcot-Marie-Tooth disease with a new mutation (Thr191Ala) in

the connexin32]

Kobari M, Irie J, Takizawa K, Yoshihara T, Sobue G.

Department of Neurology, Tachikawa Hospital.

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.