J Clin Neurol.  2007 Mar;3(1):38-44. 10.3988/jcn.2007.3.1.38.

Anticipation and Phenotypic Heterogeneity in Korean Familial Amyotrophic Lateral Sclerosis with Superoxide Dismutase 1 Gene Mutation

Affiliations
  • 1Department of Neurology, The Catholic University of Korea, Seoul, Korea. neuronet@catholic.ac.kr
  • 2Catholic Neuroscience Center, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Pharmacology, The Catholic University of Korea, Seoul, Korea.

Abstract

BACKGROUND AND PURPOSE
Different mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported in approximately 10% of cases of familial amyotrophic lateral sclerosis (ALS). The aim of this study was to analyze for mutations in the SOD1 gene and clinical characteristics in Korean family of ALS.
METHODS
A subpopulation of the family reported here has been described previously. In the present study, we analyzed the SOD1 gene in the proband and his immediate family members, who were not reported on previously. Genomic DNA was isolated from the leukocytes of whole blood samples and the coding region of the SOD1 gene was analyzed by PCR and direct sequencing.
RESULTS
The genetic alterations were a GGC-to-GTT transition at codon 10 in exon 1 and [IVS4+15_16insA; IVS4+42delG; IVS4+59_60insT] in intron 4. Patients with these mutations exhibit diverse clinical onset symptoms and acceleration of the age at onset in successive generations, which is called anticipation.
CONCLUSIONS
We have described a family with familial ALS that showed autosomal-dominant inheritance and two distinct genetic alterations in Cu/Zn-SOD1. The affected family members had different phenotypes and anticipation.

Keyword

Familial amyotrophic lateral sclerosis; Superoxide dismutase 1 (SOD1) gene; Anticipation

MeSH Terms

Acceleration
Amyotrophic Lateral Sclerosis*
Clinical Coding
Codon
DNA
Exons
Family Characteristics
Humans
Introns
Leukocytes
Phenotype
Polymerase Chain Reaction
Population Characteristics*
Superoxide Dismutase*
Superoxides*
Wills
Codon
DNA
Superoxide Dismutase
Superoxides

Figure

  • Figure 1 Pedigree of the family. Squares represent males and circles represent females. Filled symbols represent those affected with ALS. Oblique lines represent deceased family members. The arrow indicates the proband. Each mark represents the result of genetic testing as follows: *indicates carriers of the heterozygous G10V mutation plus intronic alterations of the SOD1 gene. †indicates an individual who tested positive for the intronic alterations alone. ‡indicates individuals who showed normal sequences of the SOD1 gene. §indicates an individual who has been previously described as being positive for the G10V mutation.15

  • Figure 2 Automated sequence analysis of exon 1 and intron 4 from the SOD1 gene showing the heterozygous G10V mutation and intronic alterations, respectively. The panel shows a GGC-to-GTT transition (arrow) that resulted in the substitution of valine for glycine (A) and non-amino-acid-altering variations [IVS4+15_16insA; IVS4+ 42delG; IVS4+59_60insT] in intron 4 (B). Green lines; adenine residues (A), blue lines; cytosine (C), black lines; guanine (G), red lines; thymine (T).


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