De novo variants in TCF7L2 are associated with a syndromic neurodevelopmental disorder.

ABSTRACT: TCF7L2 encodes transcription factor 7-like 2 (OMIM 602228), a key mediator of the evolutionary conserved canonical Wnt signaling pathway. Although several large-scale sequencing studies have implicated TCF7L2 in intellectual disability and autism, both the genetic mechanism and clinical phenotype have remained incompletely characterized. We present here a comprehensive genetic and phenotypic description of 11 individuals who have been identified to carry de novo variants in TCF7L2, both truncating and missense. Missense variation is clustered in or near a high mobility group box domain, involving this region in these variants' pathogenicity. All affected individuals present with developmental delays in childhood, but most ultimately achieved normal intelligence or had only mild intellectua

SUBMITTER: Dias C 

PROVIDER: S-EPMC8815108 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature