KAT6A mutations in Arboleda-Tham syndrome affect regulation and expression of HOXC genes [ATAC-seq]

Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo truncating mutations in the gene KAT6A (Lysine(K) acetyltransferase 6A). ARTHS is clinically heterogeneous but characterized by several common features including intellectual disability, developmental and speech delay, hypotonia, congenital heart defects and gastrointestinal problems. KAT6A mRNA is highly expressed throughout early development and the levels of expression are lower levels in differentiated tissues, suggesting a key role maintenance of the stem cell characteristics. Across these cell types, the gene-regulatory mechanisms controlled by KAT6A and the histone-acetylation complex in which it works remain unknown. In this study, we created ARTHS patient-derived (n=7) and control (n=13) dermal fibroblasts from skin punch biopsies. KAT6A is expressed at moderate levels in human fibroblast cells and we performed a comprehensive profiling of the epigenomic and transcriptomic changes in ARTHS. In this study, we created ARTHS patient-derived (n=7) and control (n=13) dermal fibroblasts from skin punch biopsies and performed multiomic profiling of these samples.