Clinical characteristics of familial amyotrophic lateral sclerosis with Cu/Zn superoxide dismutase gene mutations

Koji Abe, M. Aoki, M. Ikeda, M. Watanabe, S. Hirai, Y. Itoyama

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

We report clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with 4 different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene, that result in amino acid substitutions of histidine46 by arginine (H46R), leucine84 by valine (L84V), isoleucine104 by phenylalanine (I104F), and valine148 by isoleucine (V148I), in 5 Japanese families. Although features of progressive neurogenic muscular atrophy were common in patients of these families, patients of each family showed characteristic clinical features. FALS patients with the H46R mutation showed a benign clinical course and stereotype progression of muscular weakness and atrophy beginning from the legs. In FALS with the L84V mutation, while the clinical course of the disease was similar, the age at onset was younger in men than women. The patients with I104F showed wide ranges of age at onset and duration with ophthalmoparesis and sensory involvement in one patient. Those with the V148I mutation showed younger age at onset and variable first symptoms within the family. Although lower motor sign was evident in all cases, hyperreflexia varied from 0 to 100% among patients with the different mutations, and the Babinski sign was not observed in any case. Bulbar palsy was frequent with I104F, but not with H46R. SOD activity of the red blood cells was severely reduced with I104F and V148I, but was slightly reduced with H46R. These results suggest that familial ALS with different mutations of the Cu/Zn SOD gene each showed clinical characteristics, and that genetic mutations and clinical features are well correlated in familial ALS.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalJournal of the Neurological Sciences
Volume136
Issue number1-2
DOIs
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Mutation
Isoleucine
Age of Onset
Genes
Muscular Atrophy
Valine
Progressive Bulbar Palsy
Babinski's Reflex
Spinal Muscular Atrophy
Ophthalmoplegia
Abnormal Reflexes
Muscle Weakness
Missense Mutation
Amino Acid Substitution
Phenylalanine
Point Mutation
Superoxide Dismutase
Arginine
Amyotrophic lateral sclerosis 1
Superoxide Dismutase-1

Keywords

  • Amyotrophic lateral sclerosis
  • Familial
  • The Cu/Zn SOD gene

ASJC Scopus subject areas

  • Ageing
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

Clinical characteristics of familial amyotrophic lateral sclerosis with Cu/Zn superoxide dismutase gene mutations. / Abe, Koji; Aoki, M.; Ikeda, M.; Watanabe, M.; Hirai, S.; Itoyama, Y.

In: Journal of the Neurological Sciences, Vol. 136, No. 1-2, 1996, p. 108-116.

Research output: Contribution to journalArticle

Abe, Koji ; Aoki, M. ; Ikeda, M. ; Watanabe, M. ; Hirai, S. ; Itoyama, Y. / Clinical characteristics of familial amyotrophic lateral sclerosis with Cu/Zn superoxide dismutase gene mutations. In: Journal of the Neurological Sciences. 1996 ; Vol. 136, No. 1-2. pp. 108-116.
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N2 - We report clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with 4 different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene, that result in amino acid substitutions of histidine46 by arginine (H46R), leucine84 by valine (L84V), isoleucine104 by phenylalanine (I104F), and valine148 by isoleucine (V148I), in 5 Japanese families. Although features of progressive neurogenic muscular atrophy were common in patients of these families, patients of each family showed characteristic clinical features. FALS patients with the H46R mutation showed a benign clinical course and stereotype progression of muscular weakness and atrophy beginning from the legs. In FALS with the L84V mutation, while the clinical course of the disease was similar, the age at onset was younger in men than women. The patients with I104F showed wide ranges of age at onset and duration with ophthalmoparesis and sensory involvement in one patient. Those with the V148I mutation showed younger age at onset and variable first symptoms within the family. Although lower motor sign was evident in all cases, hyperreflexia varied from 0 to 100% among patients with the different mutations, and the Babinski sign was not observed in any case. Bulbar palsy was frequent with I104F, but not with H46R. SOD activity of the red blood cells was severely reduced with I104F and V148I, but was slightly reduced with H46R. These results suggest that familial ALS with different mutations of the Cu/Zn SOD gene each showed clinical characteristics, and that genetic mutations and clinical features are well correlated in familial ALS.

AB - We report clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with 4 different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene, that result in amino acid substitutions of histidine46 by arginine (H46R), leucine84 by valine (L84V), isoleucine104 by phenylalanine (I104F), and valine148 by isoleucine (V148I), in 5 Japanese families. Although features of progressive neurogenic muscular atrophy were common in patients of these families, patients of each family showed characteristic clinical features. FALS patients with the H46R mutation showed a benign clinical course and stereotype progression of muscular weakness and atrophy beginning from the legs. In FALS with the L84V mutation, while the clinical course of the disease was similar, the age at onset was younger in men than women. The patients with I104F showed wide ranges of age at onset and duration with ophthalmoparesis and sensory involvement in one patient. Those with the V148I mutation showed younger age at onset and variable first symptoms within the family. Although lower motor sign was evident in all cases, hyperreflexia varied from 0 to 100% among patients with the different mutations, and the Babinski sign was not observed in any case. Bulbar palsy was frequent with I104F, but not with H46R. SOD activity of the red blood cells was severely reduced with I104F and V148I, but was slightly reduced with H46R. These results suggest that familial ALS with different mutations of the Cu/Zn SOD gene each showed clinical characteristics, and that genetic mutations and clinical features are well correlated in familial ALS.

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