New Type X + CNS Research - from Japan

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Abstract from Acta Neurol Scand 2003 Jan;107(1):31-7

Gap junction protein beta 1 (GJB1) mutations and central nervous system

symptoms in X-linked Charcot-Marie-Tooth disease.

Takashima H, Nakagawa M, Umehara F, Hirata K, Suehara M, Mayumi H,

Yoshishige K, Matsuyama W, Saito M, Jonosono M, Arimura K, Osame M.

Third Department of Internal Medicine, Kagoshima University Faculty of

Medicine, Kagoshima 890-8520, Japan; Division of Neurology, National

Sanatorium Okinawa Hospital, Ginowan 901-2214, Japan.

Objectives - To clarify the clinical variability, including central

nervous system (CNS) involvement, in X-linked Charcot-Marie-Tooth

disease (CMTX) patients.

Materials and methods - We clinically, pathologically and genetically

studied six CMTX patients with distinct symptoms and four different GJB1

mutations.

Results - One patient with Val63Ile had deafness, low intelligence,

saccadic eye movement, upper extremity distal dominant muscle weakness

and normal sensation. Another patient with Glu186Lys had severe

sensorineural deafness at the age of 6 years, but did not develop muscle

weakness until the age of 20 years. Two patients

with Arg22Gln had typical CMT1A-like clinical features, no CNS symptoms

and obvious onion bulb formations. Two siblings with deletion of the

entire GJB1 gene had mild to moderate lower extremity muscle weakness

and sensory disturbance without CNS involvement.

Conclusion - These findings suggest that some gain of function mutations

of GJB1 may be related to CNS symptoms because the patients with GJB1

deletion only had peripheral neuropathy, although other unknown

associated factors may contribute to their clinical phenotypes.