The recurrent TCF4 missense variant p.(Arg389Cys) causes a neurodevelopmental disorder overlapping with but not typical for Pitt-Hopkins syndrome.

ABSTRACT: TCF4 haploinsufficiency by deletions, truncating variants or loss-of-function missense variants within the DNA-binding and protein interacting bHLH domain causes Pitt-Hopkins syndrome (PTHS). This neurodevelopmental disorder (NDD) is characterized by severe intellectual disability (ID), epilepsy, hyperbreathing and a typical facial gestalt. Only few aberrations of the N-terminus of TCF4 were associated with milder or atypical phenotypes. By personal communication and searching databases we assembled six cases with the novel, recurrent, de novo missense variant c.1165C > T, p.(Arg389Cys) in TCF4. This variant was identified by diagnostic exome or panel sequencing and is located upstream of the bHLH domain. All six individuals presented with moderate to severe ID with language impairment.

SUBMITTER: Popp B 

PROVIDER: S-EPMC10108566 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature