Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Institute for Advanced Research, Nagoya University, Nagoya, Aichi, Japan.
Sci Rep. 2016 Sep 12;6:33311. doi: 10.1038/srep33311.
N-methyl-d-aspartate receptors (NMDARs) play a critical role in excitatory synaptic transmission and plasticity in the central nervous systems. Recent genetics studies in schizophrenia (SCZ) show that SCZ is susceptible to NMDARs and the NMDAR signaling complex. In autism spectrum disorder (ASD), several studies report dysregulation of NMDARs as a risk factor for ASD. To further examine the association between NMDARs and SCZ/ASD development, we conducted a mutation screening study of GRIN2B which encodes NR2B subunit of NMDARs, to identify rare mutations that potentially cause diseases, in SCZ and ASD patients (n = 574 and 152, respectively). This was followed by an association study in a large sample set of SCZ, ASD, and normal healthy controls (n = 4145, 381, and 4432, respectively). We identified five rare missense mutations through the mutation screening of GRIN2B. Although no statistically significant association between any single mutation and SCZ or ASD was found, one of its variant, K1292R, is found only in the patient group. To further examine the association between mutations in GRIN2B and SCZ/ASD development, a larger sample size and functional experiments are needed.
N-甲基-D-天冬氨酸受体（NMDARs）在中枢神经系统的兴奋性突触传递和可塑性中发挥着关键作用。最近的精神分裂症（SCZ）遗传学研究表明，SCZ易受 NMDARs 和 NMDAR 信号复合物的影响。在自闭症谱系障碍（ASD）中，几项研究报告 NMDARs 的失调是 ASD 的一个风险因素。为了进一步研究 NMDARs 与 SCZ/ASD 发展之间的关系，我们对编码 NMDARs 的 NR2B 亚基的 GRIN2B 进行了突变筛选研究，以鉴定可能导致疾病的罕见突变，在 SCZ 和 ASD 患者中（分别为 n=574 和 152）。随后在 SCZ、ASD 和正常健康对照者的大样本集中进行了关联研究（n=4145、381 和 4432）。我们通过 GRIN2B 的突变筛选发现了五个罕见的错义突变。虽然没有发现任何单个突变与 SCZ 或 ASD 之间存在统计学上的显著关联，但它的一个变体 K1292R 只存在于患者组中。为了进一步研究 GRIN2B 突变与 SCZ/ASD 发展之间的关系，需要更大的样本量和功能实验。
