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.
Design: 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.