Abstract：
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.
摘要：
GTF2IRD1是染色体7上编码转录因子的基因,由于其杂合丢失是与Williams-Beuren综合征（WBS）相关的经典缺失的一部分，因此具有重要的临床意义。然而,GTF2IRD1中的双等位基因变异体单独作为常染色体隐性遗传疾病的一部分尚未被报道。这里,我们提出了两个完整的兄弟，它们具有GTF2IRD1的反式变体，c.1231C>T（p。Arg411Trp）和c.2632C>G（p。Leu878Val）。描述了详细的临床表型，其中包括严重的神经发育障碍，面部畸形,和漏斗胸.重要的是,在八个完整的兄弟姐妹中，只有这两个兄弟具有反式的两种变体，才具有深刻描述的表型。我们提出了这些兄弟代表以GTF2IRD1中的双等位基因变体为特征的新综合征的鉴定的可能性，这也可能对WBS的分子病因具有重要意义。
