Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family.
BACKGROUND
A family with a complicated constellation of neurologic findings, including neuropathy, myotonia, and periodic paralysis, has been described in 4 studies in the medical literature since 1934. The underlying cause of their disease has been the subject of considerable speculation and has never been identified until now.


OBJECTIVE
To identify the molecular basis of this family's neurologic disease.


METHODS
The coding regions of 6 genes that cause peripheral neuropathy and regions of the muscle sodium channel gene (SCN4A) were sequenced.


RESULTS
A novel missense mutation (Arg67Pro) in the myelin protein zero gene was identified in 2 patients with Charcot-Marie-Tooth disease, and a common missense mutation (Thr704Met) was identified in the SCN4A gene in 4 family members. We discuss the difficulties of genotype-phenotype correlation in this family.


CONCLUSIONS
These findings indicate that 2 independent mutations segregating in this family are responsible for the puzzling clinical picture.
Hisama
Fuki M
FM
Department of Neurology, Neurogenetics Program, Yale University School of Medicine, 333 Cedar Street, PO Box 208018, New Haven, CT 06520-8018, USA. fuki.hisama@yale.edu
D000293:Adolescent; D016022:Case-Control Studies; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D012189:Retrospective Studies; D015222:Sodium Channels / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C115628:MPZL1 protein, human; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010750:Phosphoproteins; C106251:SCN4A protein, human; D015222:Sodium Channels