Rare loss of function mutations in N-methyl-d-aspartate glutamate receptors and their contributions to schizophrenia susceptibility
| Autor: | Masaki Kodaira, Kanako Ishizuka, Manabu Takaki, Yingni Lin, Jun Egawa, Jingrui Xing, Masahide Usami, Miho Toyama, Shinji Sakamoto, Akira Yoshimi, Kinji Ohno, Tomoko Oya-Ito, Yota Uno, Masashi Ikeda, Mako Morikawa, Nakao Iwata, Takashi Okada, Itaru Kushima, Toshiyuki Someya, Yuto Takasaki, Daisuke Mori, Hiroki Kimura, Yuko Arioka, Yuko Okahisa, Branko Aleksic, Yukako Nakamura, Tomoko Shiino, Yanjie Yu, Norio Ozaki, Chenyao Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent Autism Spectrum Disorder Receptors N-Methyl-D-Aspartate Article Frameshift mutation lcsh:RC321-571 Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Loss of Function Mutation mental disorders Humans Missense mutation Genetic Predisposition to Disease GRIN3A Child lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Loss function Genetics Splice site mutation biology GRIN1 Exons Middle Aged Psychiatry and Mental health 030104 developmental biology Case-Control Studies Schizophrenia biology.protein GRIN2A Female 030217 neurology & neurosurgery Minigene |
| Zdroj: | Translational Psychiatry, Vol 8, Iss 1, Pp 1-9 (2018) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | In schizophrenia (SCZ) and autism spectrum disorder (ASD), the dysregulation of glutamate transmission through N-methyl-d-aspartate receptors (NMDARs) has been implicated as a potential etiological mechanism. Previous studies have accumulated evidence supporting NMDAR-encoding genes' role in etiology of SCZ and ASD. We performed a screening study for exonic regions of GRIN1, GRIN2A, GRIN2C, GRIN2D, GRIN3A, and GRIN3B, which encode NMDAR subunits, in 562 participates (370 SCZ and 192 ASD). Forty rare variants were identified including 38 missense, 1 frameshift mutation in GRIN2C and 1 splice site mutation in GRIN2D. We conducted in silico analysis for all variants and detected seven missense variants with deleterious prediction. De novo analysis was conducted if pedigree samples were available. The splice site mutation in GRIN2D is predicted to result in intron retention by minigene assay. Furthermore, the frameshift mutation in GRIN2C and splice site mutation in GRIN2D were genotyped in an independent sample set comprising 1877 SCZ cases, 382 ASD cases, and 2040 controls. Both of them were revealed to be singleton. Our study gives evidence in support of the view that ultra-rare variants with loss of function (frameshift, nonsense or splice site) in NMDARs genes may contribute to possible risk of SCZ. |
| Databáze: | OpenAIRE |
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