Novel deletion mutations of OPTN in amyotrophic lateral sclerosis in Japanese

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.