Thus far, a handful of highly penetrant mutations conferring risk of psychosis have been discovered. Here we used whole-genome sequencing and long-range phasing to investigate an Icelandic kindred containing ten individuals with psychosis (schizophrenia, schizoaffective disorder or psychotic bipolar disorder). We found that all affected individuals carry RBM12 (RNA-binding-motif protein 12) c.2377G>T (P = 2.2 × 10^-4), a nonsense mutation that results in the production of a truncated protein lacking a predicted RNA-recognition motif. We replicated the association in a Finnish family in which a second RBM12 truncating mutation (c.2532delT) segregates with psychosis (P = 0.020). c.2377G>T is not fully penetrant for psychosis; however, we found that carriers unaffected by psychosis resemble patients with schizophrenia in their non-psychotic psychiatric disorder and neuropsychological test profile (P = 0.0043) as well as in their life outcomes (including an increased chance of receiving disability benefits, P = 0.011). As RBM12 has not previously been linked to psychosis, this work provides new insight into psychiatric disease.

中文翻译：

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RBM12中的截短突变与精神病有关。

迄今为止，已经发现了少数几种赋予精神病风险的高度渗透性突变。在这里，我们使用全基因组测序和远距离定相研究了一个冰岛亲属，其中有十个人患有精神病（精神分裂症，分裂情感障碍或精神病性双相情感障碍）。我们发现所有受影响的个体均携带RBM12（RNA结合基序蛋白12）c.2377G> T（P = 2.2×10 ^-4），这是一种无意义的突变，可导致产生缺少预测的RNA识别基序的截短的蛋白质。我们在一个芬兰家庭中复制了这种关联，其中第二个RBM12截短突变（c.2532delT）与精神病隔离（P = 0.020）。c.2377G> T不能完全渗透精神病；但是，我们发现未受到精神病影响的携带者在非精神病性精神疾病和神经心理测试特征（P = 0.0043）以及生活结局（包括增加的获得残疾津贴的机会增加，P = 0.011）方面类似于精神分裂症患者。 。由于RBM12以前与精神病没有关联，因此这项工作为精神病学提供了新的见解。