Rare compound heterozygous missense SPATA7 variations and risk of schizophrenia; whole-exome sequencing in a consanguineous family with affected siblings, follow-up sequencing and a case-control study

• Published in: Neuropsychiatric disease and treatment 2019-08, Vol.15, p.2353-2363
• Main Authors: Igeta, Hirofumi, Watanabe, Yuichiro, Morikawa, Ryo, Ikeda, Masashi, Otsuka, Ikuo, Hoya, Satoshi, Koizumi, Masataka, Egawa, Jun, Hishimoto, Akitoyo, Iwata, Nakao, Someya, Toshiyuki
• Format: Article
• Language: English
• Subjects: Deoxyribonucleic acid; DNA; Family; Females; Genes; Genomes; Glycine; Haplotypes; Japanese; Mental disorders; multiplex schizophrenia family; next-generation sequencing; Offspring; Original Research; Parenting; Parents & parenting; Postpartum depression; recessive variations; Schizophrenia; Siblings; Variation
• ISSN: 1176-6328; 1178-2021; 1178-2021
• DOI: 10.2147/ndt.s218773

Whole-exome sequencing (WES) of multiplex families is a promising strategy for identifying causative variations for common diseases. To identify rare recessive risk variations for schizophrenia, we performed a WES study in a consanguineous family with affected siblings. We then performed follow-up sequencing of in schizophrenia-affected families. In addition, we performed a case-control study to investigate association between variations and schizophrenia. WES was performed on two affected siblings and their unaffected parents, who were second cousins, of a multiplex schizophrenia family. Subsequently, we sequenced the coding region of , a potential risk gene identified by the WES analysis, in 142 affected offspring from 137 families for whom parental DNA samples were available. We further tested rare recessive variations, identified by WES and sequencing, for associations with schizophrenia in 2,756 patients and 2,646 controls. Our WES analysis identified rare compound heterozygous missense variations, p.Asp134Gly and p.Ile332Thr, in both affected siblings. Sequencing coding regions from 137 families identified no rare recessive variations in affected offspring. In the case-control study, we did not detect the rare compound heterozygous missense variations in patients or controls. Our data does not support the role of the rare compound heterozygous missense variations p.Asp134Gly and p.Ile332Thr in conferring a substantial risk of schizophrenia.