J Korean Neurol Assoc > Volume 20(4); 2002 > Article

Journal of the Korean Neurological Association 2002;20(4): 379-384.

"가족성 근위축성측삭경화증 환자에서 새로이 발견된 SOD1 유전자 돌연변이 Gly10Val."

김남희, "김현정 홍윤호 김한준 전종은 성정준 권오현 김성훈 박경석 김만호 이광우 박성호"

"서울대학교 의과대학 신경과학교실,서울대학 병원 임상연구소 신경과학교실,을지의과대학교 신경과학교실* 강원대학교 의과대학 신경과학교실,인제대학교 의과대학 저동 백병원 신경과학교실, 서울 특별시립 보라매병원 신경과학교실"

"Korean Familial Amyotrophic Lateral Sclerosis Family with a Novel Gly10Val Mutation in the SOD1 Gene"

Nam-Hee Kim

Department of Neurology, Seoul Natiotnal University, Clinical Research Institute, Neuroscience Center, and Biomedical Research Center, Korean National Institute of Health, Gang-Won University, In-Jae University

Abstract

"Background : Approximately 5 to 10% of amyotrophic lateral sclerosis (ALS) patients have recorded family history (FALS) and in most cases, the pattern of inheritance is autosomal dominant (DFALS). Twenty percent of DFALS fami-lies are linked to chromosome 21q22.1, which is associated to a mutation in the Cu/Zn superoxide dismutase (SOD1) gene. However, these cases, especially with SOD1 gene mutations have not yet been reported in Korea. We investigated the clinical features of familial ALS pedigrees and screened the SOD1 gene in search of potential mutations. Methods : The clinical histories and neurological findings of the family members were obtained. Genomic DNA was extracted from leukocytes of whole blood samples and PCR and direct sequencing analyzed the coding region of the SOD1 gene. Results : Five affected members in a three-generation family exhibited early onset and rapid progression. The family has a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation GGC to GTT, causing a substitution of valine for glycine at codon 10 (Gly10Val) in exon 1. Conclusions : Familial ALS with a novel Gly10Val mutation in the SOD1 gene showed severe clinical features. The mutation lies in a region involved in a dimer contact in the third-dimensional structure of the SOD1 protein. This study is the first report of familial ALS cases in Korea and contributes to expand the number of ALS-associated SOD1 gene mutations.Key Words : Amyotrophic lateral sclerosis, SOD1, Mutation, Korean family"