title: Novel deletion mutations of OPTN in amyotrophic lateral sclerosis in Japanese.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron death in the brain and spinal cord. Many disease genes for ALS have been identified; however, each disease gene is responsible for very small fractions of ALS. Recently, mutations of the gene encoding optineurin (OPTN) are reported in familial and sporadic ALS. OPTN is also responsible for a small number of ALS, 3.8% of familial and 0.29% of sporadic ALS in Japanese. The low prevalence may be an underestimation due to incomplete screening of the mutation. To examine OPTN mutations more extensively, we screened the OPTN deletions using a quantitative PCR system. We examined 710 Japanese ALS subjects who had previously been found to have no OPTN mutations by a screening using a PCR-direct sequence strategy. We identified 3 kinds of deletions in 5 patients; one was homozygous, and the remaining were heterozygous. All deletions occurred due to the Alu-mediated recombination and are expected to result in null alleles. Our results suggest that the OPTN deletion mutation in ALS is not infrequent and the prevalence of the OPTN mutation in Japanese sporadic ALS is considerably high.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Motoki
authors.initials: M
authors.lastname: Sano
authors.forename: Tetsumasa
authors.initials: T
authors.lastname: Kamei
authors.forename: Shuichi
authors.initials: S
authors.lastname: Oshima
authors.forename: Torao
authors.initials: T
authors.lastname: Tokuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D018797:Cell Cycle Proteins; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D026901:Membrane Transport Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D005819:Genetic Markers; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA