Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset before 13 years of age. There is rising evidence that genetic factors play a major role in COS etiology, yet, only a few single gene mutations have been discovered. Here we present a diagnostic whole-exome sequencing (WES) in an Israeli Jewish female with COS and additional neuropsychiatric conditions such as obsessive-compulsive disorder (OCD), anxiety, and aggressive behavior. Variant analysis revealed a de novo novel stop gained variant in GRIA2 gene (NM_000826.4: c.1522 G > T (p.Glu508Ter)). GRIA2 encodes for a subunit of the AMPA sensitive glutamate receptor (GluA2) that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. GluA2 subunit mutations are known to cause variable neurodevelopmental phenotypes including intellectual disability, autism spectrum disorder, epilepsy, and OCD. Our findings support the potential diagnostic role of WES in COS, identify GRIA2 as possible cause to a broad psychiatric phenotype that includes COS as a major manifestation and expand the previously reported GRIA2 loss of function phenotypes.

儿童期精神分裂症（COS）是一种罕见的精神分裂症，发病于13岁之前。越来越多的证据表明遗传因素在COS病因中起着重要作用，但是，仅发现了少数几个单基因突变。在这里，我们介绍了一名以色列犹太女性的诊断性全外显子测序（WES），其患有COS和其他神经精神疾病，例如强迫症（OCD），焦虑症和攻击行为。变异分析显示，GRIA2基因从头开始获得了新的终止变异（NM_000826.4：c.1522 G> T（p.Glu508Ter））。GRIA2编码AMPA敏感谷氨酸受体（GluA2）的一个亚基，在中枢神经系统中起配体门控离子通道的作用，并在兴奋性突触传递中起重要作用。已知GluA2亚基突变会引起可变的神经发育表型，包括智力残疾，自闭症谱系障碍，癫痫和强迫症。我们的发现支持WES在COS中的潜在诊断作用，将GRIA2鉴定为广泛的精神病表型（包括COS作为主要表现形式）的可能原因，并扩展了先前报道的GRIA2功能表型丧失。