Neuropsychiatric Disease and Treatment (2019-08-01)

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

  • Igeta H,
  • Watanabe Y,
  • Morikawa R,
  • Ikeda M,
  • Otsuka I,
  • Hoya S,
  • Koizumi M,
  • Egawa J,
  • Hishimoto A,
  • Iwata N,
  • Someya T

Journal volume & issue
Vol. Volume 15
pp. 2353 – 2363


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Hirofumi Igeta,1 Yuichiro Watanabe,1 Ryo Morikawa,1 Masashi Ikeda,2 Ikuo Otsuka,3 Satoshi Hoya,1 Masataka Koizumi,1 Jun Egawa,1 Akitoyo Hishimoto,3 Nakao Iwata,2 Toshiyuki Someya11Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 2Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 3Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, JapanCorrespondence: Yuichiro WatanabeDepartment of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, Chuo-ku, Niigata 951-8510, JapanTel +81 25 227 2213Fax +81 25 227 0777Email [email protected]: 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 SPATA7 in schizophrenia-affected families. In addition, we performed a case-control study to investigate association between SPATA7 variations and schizophrenia.Patients and methods: 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 SPATA7, 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 SPATA7 variations, identified by WES and sequencing, for associations with schizophrenia in 2,756 patients and 2,646 controls.Results: Our WES analysis identified rare compound heterozygous missense SPATA7 variations, p.Asp134Gly and p.Ile332Thr, in both affected siblings. Sequencing SPATA7 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 SPATA7 missense variations in patients or controls.Conclusion: Our data does not support the role of the rare compound heterozygous SPATA7 missense variations p.Asp134Gly and p.Ile332Thr in conferring a substantial risk of schizophrenia.Keywords: Japanese, multiplex schizophrenia family, next-generation sequencing, recessive variations