School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou, China.
School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou, China; The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Gene. 2023 Nov 30;886:147777. doi: 10.1016/j.gene.2023.147777. Epub 2023 Sep 6.
The TBL1XR1 gene encodes the protein transducin-beta-like 1 receptor1, widely distributed in the pituitary, hypothalamus, white and brown adipose tissue, muscle, and liver. Current evidence suggests that heterozygous TBL1XR1 pathogenic variants can lead to a wide spectrum of phenotypes. This study aims to reveal the clinical phenotype and genetic profiles of de novo TBL1XR1 variations and summarize the relevant clinical and genetic features.
We analyzed four new cases harboring de novo TBL1XR1 variants and reviewed all reported cases.
All probands suffered from global developmental delay. Moreover, patient 1 exhibited susceptibility to startle, patient 2 had hypovitaminosis D, short stature and hyponatremia, and patients 3 and 4 both presented with ASD (Autism spectrum disorder) and short stature. They all had a de novo TBL1XR1 variant (NM_024665.7), c.1184A > G (p.Tyr395Cys), c.1108G > A (p.Asp370Asn), c.1047 + 1G > C, and c.1097C > T (p.Ser366Phe) respectively. In addition, pooled analysis of 51 cases showed that they had speech impairment (38/39), intellectual developmental disorder (28/28), global developmental delay (42/42), and hypotonia (24/27), and some of them had epilepsy (10/22), ASD (13/25), and developmental regression (4/13).
We report four new patients with de novo TBL1XR1 variants and provide a comprehensive overview of 47 previously reported individuals with TBL1XR1 variants, enriching the genotypic and phenotypic spectrum of TBL1XR1-related disease. This report further validates the pathogenicity de novo TBL1XR1 variants.
TBL1XR1 基因编码跨膜蛋白-β样 1 受体 1，广泛分布于垂体、下丘脑、白色和棕色脂肪组织、肌肉和肝脏中。目前的证据表明，杂合 TBL1XR1 致病性变异可导致广泛的表型。本研究旨在揭示 TBL1XR1 变异的新生突变的临床表型和遗传特征，并总结相关的临床和遗传特征。
我们分析了 4 例携带新生 TBL1XR1 变异的新病例，并回顾了所有报道的病例。
所有先证者均有全面发育迟缓。此外，患者 1 易受惊吓，患者 2 有维生素 D 缺乏症、身材矮小和低钠血症，患者 3 和 4 均有 ASD（自闭症谱系障碍）和身材矮小。他们均携带 TBL1XR1 变异（NM_024665.7），c.1184A>G（p.Tyr395Cys），c.1108G>A（p.Asp370Asn），c.1047+1G>C 和 c.1097C>T（p.Ser366Phe）。此外，51 例病例的汇总分析显示，他们存在言语障碍（38/39）、智力发育障碍（28/28）、全面发育迟缓（42/42）和肌张力低下（24/27），其中一些存在癫痫（10/22）、ASD（13/25）和发育倒退（4/13）。
我们报道了 4 例携带新生 TBL1XR1 变异的新患者，并对 47 例报道的 TBL1XR1 变异患者进行了全面概述，丰富了 TBL1XR1 相关疾病的基因型和表型谱。本报告进一步验证了新生 TBL1XR1 变异的致病性。
