Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

ABSTRACT: Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical f

SUBMITTER: Sheppard SE 

PROVIDER: S-EPMC10005179 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature