A clinical variance in familial amyotrophic lateral sclerosis with a point mutation in Cu/Zn superoxide dismutase gene

R. Sakuma, Koji Abe, M. Aoki, M. Ikeda, N. Okita, M. Hiwatari, M. Sakurai, Y. Itoyama

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

We report here a novel point mutation in exon 5 of the Cu/Zn superoxide dismutase (SOD) gene resulting in an amino acid substitution of valine148 by isoleucine (V148I) in a Japanese family with amyotrophic lateral sclerosis (FALS). In this family, the age at onset was young (28.0 ± 3.8 years old, mean ± SD, n = 4) and the disease progression was rapid (22.0 ± 5.9 months, n = 3) with low Cu/Zn SOD activity (56.3 and 59.0% of the controls, n = 2). It is interesting that the clinical features of ALS varied very much among the affected members. One case had weakness of the lower extremities at first, and died without bulbar paresis. The second case first noticed wasting of the upper limbs with bulbar symptoms, but the third had weakness of upper extremities without developing dysarthria nor dysphagia until death. The living remainder first developed fasciculation of the tongue without weakness of extremities. The valine148 is conserved among different species, and V148I mutation might destabilize dimer formation with another SOD subunit, leading to decrease enzymatic activity. These results suggested that there could be considerable clinical variance among the patients of FALS within one family, carrying the same Cu/Zn SOD mutation such as V148I. 1995 Lippincott Williams & Wilkins

Original languageEnglish
Pages (from-to)369-374
Number of pages6
JournalEuropean Journal of Neurology
Volume2
Issue number4
DOIs
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Point Mutation
Isoleucine
Amyotrophic Lateral Sclerosis
Upper Extremity
Genes
Fasciculation
Dysarthria
Mutation
Paresis
Amino Acid Substitution
Deglutition Disorders
Age of Onset
Superoxide Dismutase
Disease Progression
Lower Extremity
Exons
Extremities
Amyotrophic lateral sclerosis 1
Superoxide Dismutase-1

Keywords

  • ALS
  • Cu/Zn SOD
  • Familial
  • Point mutation
  • V148I

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

A clinical variance in familial amyotrophic lateral sclerosis with a point mutation in Cu/Zn superoxide dismutase gene. / Sakuma, R.; Abe, Koji; Aoki, M.; Ikeda, M.; Okita, N.; Hiwatari, M.; Sakurai, M.; Itoyama, Y.

In: European Journal of Neurology, Vol. 2, No. 4, 1995, p. 369-374.

Research output: Contribution to journalReview article

Sakuma, R. ; Abe, Koji ; Aoki, M. ; Ikeda, M. ; Okita, N. ; Hiwatari, M. ; Sakurai, M. ; Itoyama, Y. / A clinical variance in familial amyotrophic lateral sclerosis with a point mutation in Cu/Zn superoxide dismutase gene. In: European Journal of Neurology. 1995 ; Vol. 2, No. 4. pp. 369-374.
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AB - We report here a novel point mutation in exon 5 of the Cu/Zn superoxide dismutase (SOD) gene resulting in an amino acid substitution of valine148 by isoleucine (V148I) in a Japanese family with amyotrophic lateral sclerosis (FALS). In this family, the age at onset was young (28.0 ± 3.8 years old, mean ± SD, n = 4) and the disease progression was rapid (22.0 ± 5.9 months, n = 3) with low Cu/Zn SOD activity (56.3 and 59.0% of the controls, n = 2). It is interesting that the clinical features of ALS varied very much among the affected members. One case had weakness of the lower extremities at first, and died without bulbar paresis. The second case first noticed wasting of the upper limbs with bulbar symptoms, but the third had weakness of upper extremities without developing dysarthria nor dysphagia until death. The living remainder first developed fasciculation of the tongue without weakness of extremities. The valine148 is conserved among different species, and V148I mutation might destabilize dimer formation with another SOD subunit, leading to decrease enzymatic activity. These results suggested that there could be considerable clinical variance among the patients of FALS within one family, carrying the same Cu/Zn SOD mutation such as V148I. 1995 Lippincott Williams & Wilkins

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