Premium
Biallelic GTF2IRD1 variants in brothers with profound neurodevelopmental disorder: A possible novel disorder involving a critical gene for Williams syndrome
Author(s) -
Cummings Christopher Thomas,
Starr Lois Janelle
Publication year - 2023
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.63021
Subject(s) - genetics , phenotype , gene , neurodevelopmental disorder , biology , allele , etiology , pectus excavatum , medicine , pathology
GTF2IRD1 , a gene on chromosome 7 which encodes a transcription factor, is of significant clinical interest due to its heterozygous loss as part of the classical deletion associated with Williams–Beuren syndrome (WBS). However, biallelic variants in GTF2IRD1 alone as part of an autosomal recessive disease have not been previously reported. Here, we present two full brothers with variants in trans of GTF2IRD1 at c.1231C > T (p.Arg411Trp) and c.2632C > G (p.Leu878Val). A detailed clinical phenotype is described, which includes severe neurodevelopmental disability, facial dysmorphology, and pectus excavatum. Importantly, out of eight full siblings, only these two brothers harboring both variants in trans present with the profound described phenotype. We present the possibility that these brothers represent the identification of a new syndrome characterized by biallelic variants in GTF2IRD1 , which may also have important implications for the molecular etiology of WBS.