Anticipation and phenotypic heterogeneity in korean familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutation.
OBJECTIVE
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.
Kim
Woojun
W
Department of Neurology, The Catholic University of Korea, Seoul, Korea.
Kim
Joong-Seok
JS
Lee
Kwang-Soo
KS
Gwoun
Young-Ju
YJ
Kim
Jin-Mo
JM
Lee
Kwon-Haeng
KH