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Fuki M. Hisama, MD

Arch Neurol. 2005;62:135-138.

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.

Author Affiliation: Department of Neurology, Neurogenetics Program, Yale University School of Medicine, New Haven, Conn.