Mutational analysis of familial and sporadic amyotrophic lateral sclerosis with OPTN mutations in Japanese population.
Our objective was to elucidate the genetic epidemiology of familial amyotrophic lateral sclerosis (FALS) and sporadic ALS (SALS) with OPTN mutations in the Japanese population. Mutational analysis of OPTN was conducted in 18 FALS pedigrees in whom mutations in other causative genes have been excluded and in 218 SALS patients by direct nucleotide sequence analysis. Novel non-synonymous variants identified in ALS patients were further screened in 271 controls. Results showed that although no mutations were identified in the FALS pedigrees, a novel heterozygous non-synonymous variant c.481G > A (p.V161M) was identified in one SALS patient, who originated from the southernmost part of the Kii Peninsula. The mutation was not present in 271 controls. As the clinical feature, the patient carrying V161M showed predominantly upper motor neuron signs with slow progression. This study suggests that mutations in OPTN are not the main cause of ALS in the Japanese population.
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroya
H
Naruse
Yuji
Y
Takahashi
Tameko
T
Kihira
Sohei
S
Yoshida
Yasumasa
Y
Kokubo
Shigeki
S
Kuzuhara
Hiroyuki
H
Ishiura
Masaharu
M
Amagasa
Shigeo
S
Murayama
Shoji
S
Tsuji
Jun
J
Goto
D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000235:genetics*; D044466:Asian People; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D014633:Valine / Q000235:genetics
D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D008715:Methionine; D014633:Valine