Cohesion of Cortical Language Networks During Word Processing Is Predicted by a Common Polymorphism in the SETBP1 Gene

Abstract

The etiological mechanisms of the genetic underpinnings of developmental language disorder (DLD) are unknown, in part due to the behavioral heterogeneity of the disorder's manifestations. In this study, we explored an association between the SETBP1 gene (18q21.1), revealed in a genome‐wide association study of DLD in a geographically isolated population, and brain network‐based endophenotypes of functional intracortical coherence between major language‐related brain areas. We analyzed electroencephalogram (EEG) data from thirty‐nine children (twenty‐three with, sixteen without DLD) aged 7.17–15.83 years acquired during an auditory picture–word matching paradigm. Variation at a single nucleotide polymorphism in the intronic region of the SETBP1 gene, rs8085464, explained 19% of the variance in intracortical network cohesion (p = .00478). This suggests that the development of these brain networks might be partially associated with the variation in SETBP1.

Delayed Bone Age in a Child with a Novel Loss-of-Function Variant in <i>SETBP1</i> Gene Sheds Light on the Potential Role of SETBP1 Protein in Skeletal Development

“…While the complete range of functions of the SETBP1 protein remains unknown, it has been observed that it is widely expressed in numerous body tissues, including the brain where it is involved in regulating gene expression through the histone methylation process. Specifically, it promotes chromatin accessibility to transcription, facilitating gene activation [12]. The SETBP1 gene is composed of three adeninethymine (AT)-hook domains that encode for specific amino acid sequences: 584-596 (KKKRGRPKKQPLL), 1016-1028 (KKKRGRPAKTNDT), and 1451-1463 (KKRRGRPRKQPTQ).…”

The impact of SETBP1 mutations in neurological diseases and cancer

“…Furthermore, the loss‐of‐function mutations in SETBP1 have also been reported to be associated with intellectual disability, expressive language disorders, childhood aphasia, autism spectrum disorders, neurodevelopmental disorders, and developmental epileptic encephalopathy (Antonyan & Ernst, 2022; Coe et al, 2014; Filges et al, 2011; Jansen et al, 2021; Leonardi et al, 2020; Morgan et al, 2021; Rakhlin et al, 2020; Wong et al, 2022). These symptoms are also observed in SGS but are more severe.…”