SETD1B基因位于染色体12q24上，是参与基因转录表观遗传调控的染色质修饰基因之一。 SETD1B 基因致病性变异的表型包括智力障碍、癫痫发作和语言发育迟缓 (IDDSELD, OMIM 619000)。在这项研究中，我们介绍了一个由死于癌症的近亲父母及其后代组成的家庭。这个家庭包括两个被诊断患有自闭症谱系障碍（ASD）的病例；六例被诊断患有精神分裂症、双相情感障碍或分裂情感障碍；有确诊患有癌症的病例；另有五例在儿童早期不明原因死亡。该家庭的三名受影响成员同意进行基因检测。我们使用全外显子组测序。我们报告了一个新的 SETD1B 基因框内删除变异，该变异出现在一个被诊断为分裂情感性障碍和自闭症谱系障碍（ASD）但没有癫痫发作和智力障碍的病例的家庭中。结果发现，该表型特征在我们提出的家族中至少遗传了三代，并且表明 SETD1B 基因的致病性变异从受影响的父母遗传给了其受影响的孩子。此外，父亲被诊断患有分裂情感障碍和白血病。我们提出 SETD1B 的罕见变异与自闭症谱系障碍和不伴有癫痫发作和智力障碍的分裂情感障碍的表型之间存在关联。 SETD1B基因被收录在SFARI的ASD遗传数据库（https://gene.sfari.org/）和COSMIC的癌症数据库（https://cancer.sanger.ac.uk/cosmic）中。然而，关于 SETD1B 基因变异作为临床实体的报道却很少。据我们所知，此前尚未在被诊断患有神经精神疾病和癌症的个体中报道过 SETD1B 基因变异。© 2024 国际发育神经科学学会。

The SETD1B gene, located on chromosome 12q24, is one of the chromatin-modifying genes involved in epigenetic regulation of gene transcription. The phenotype of pathogenic variants in the SETD1B gene includes intellectual disability, seizures, and language delay (IDDSELD, OMIM 619000). In this study, we present a family consisting of consanguineous parents who died of cancer and their offspring. This family includes two cases diagnosed with autism spectrum disorder (ASD); six cases diagnosed with schizophrenia, bipolar disorder, or schizoaffective disorder; there cases diagnosed with cancer; and five cases who died of unknown causes in early childhood. Three affected members of this family agreed to genetic testing. We used whole exome sequencing. We report a novel in-frame deletion variant of the SETD1B gene in a family with cases diagnosed with schizoaffective disorder and ASD without seizures and intellectual disability. It was found that the phenotypic features were inherited for at least three generations in the family we presented, and it was shown that the pathogenic variant of the SETD1B gene was transmitted from the affected parent to his affected children. In addition, the father was diagnosed with both schizoaffective disorder and leukemia. We proposed an association between rare variants of SETD1B and phenotypes of ASD and schizoaffective disorder without seizures and intellectual disability. The SETD1B gene is included in both the ASD genetic database of SFARI (https://gene.sfari.org/) and the cancer database of COSMIC (https://cancer.sanger.ac.uk/cosmic). However, there are very few reports of SETD1B gene variants as clinical entities. To our knowledge, the SETD1B gene variant has not been previously reported in an individual diagnosed with both a neuropsychiatric disorder and cancer.© 2024 International Society for Developmental Neuroscience.