Variable clinical symptoms in familial amyotrophic lateral sclerosis with a novel point mutation in the Cu/Zn superoxide dismutase gene

M. Ikeda, Koji Abe, M. Aoki, M. Sahara, M. Watanabe, M. Shoji, P. H. St. George-Hyslop, S. Hirai, Y. Itoyama

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

We report a novel missense point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene of affected members of a Japanese kindred segregating familial amyotrophic lateral sclerosis (FALS) through at least three successive generations. The mutation, which is predicted to cause the replacement of isoleucine at codon 104 by phenylalanine (I104F), is associated with a significant reduction in Cu/Zn SOD enzyme activity but results in a highly variable clinical phenotype. Age at onset varied from 6 to 55; the initial symptoms occurred in either the lower or upper extremities in different family members. The duration of the disease varied from 3 to 38 years. Two subjects, aged 59 and 34, remained asymptomatic until their death from other causes, although their offspring carrying the same mutation have already developed clinical evidence of the disease. These results suggest that FALS from this novel I104F mutation shows considerable clinical variation.

Original languageEnglish
Pages (from-to)2038-2042
Number of pages5
JournalNeurology
Volume45
Issue number11
DOIs
Publication statusPublished - 1995 Nov

ASJC Scopus subject areas

  • Clinical Neurology

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