Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability.

ABSTRACT: Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate. ZFHX3 LoF associates with a specific methylation profile in whole blood extracted DNA. Nuclear abundance of ZFHX3 increases during human brain development and neuronal dif

SUBMITTER: Perez Baca MDR 

PROVIDER: S-EPMC10940049 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature