Gap junction protein beta 1 (GJB1) mutations and central nervous system symptoms in X-linked Charcot-Marie-Tooth disease.
OBJECTIVE
To clarify the clinical variability, including central nervous system (CNS) involvement, in X-linked Charcot-Marie-Tooth disease (CMTX) patients.


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.


CONCLUSIONS
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.
Takashima
H
H
Third Department of Internal Medicine, Kagoshima University Faculty of Medicine, Kagoshima 890-8520, Japan.
Nakagawa
M
M
Umehara
F
F
Hirata
K
K
Suehara
M
M
Mayumi
H
H
Yoshishige
K
K
Matsuyama
W
W
Saito
M
M
Jonosono
M
M
Arimura
K
K
Osame
M
M
D000328:Adult; D000368:Aged; D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000175:diagnosis / Q000235:genetics; D005500:Follow-Up Studies; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009460:Neurologic Examination; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D012729:Sex Chromosome Aberrations; D013497:Sural Nerve / Q000473:pathology; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D000097002:Gap Junction beta-1 Protein