Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling.

ABSTRACT:

Background

SETBP1 Haploinsufficiency Disorder (SETBP1-HD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive. We investigate the functional effects of three SETBP1 genetic variants including two pathogenic mutations p.Glu545Ter and SETBP1 p.Tyr1066Ter, resulting in removal of SKI and/or SET domains, and a point mutation p.Thr1387Met in the SET domain.

Methods

Genetic variants were introduced into induced pluripotent stem cells (iPSCs) and subsequently differentiated into neurons to

SUBMITTER: Shaw NC 

PROVIDER: S-EPMC11443744 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature