Fuki M Hisama1. 1. 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
Abstract
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.
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.
Authors: Ilaria Callegari; C Gemelli; A Geroldi; F Veneri; P Mandich; M D'Antonio; D Pareyson; M E Shy; A Schenone; V Prada; M Grandis Journal: J Neurol Date: 2019-07-05 Impact factor: 4.849