Phenotypes of autism spectrum disorder and schizoaffective disorder associated with SETD1B gene but without intellectual disability and seizures

Abstract

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 () and the cancer database of 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.