背景:QRICH1编码富含谷氨酰胺的蛋白1,该蛋白含有一个胱天蛋白酶激活募集结构域,可能参与细胞凋亡和炎症。然而,QRICH1基因的功能在很大程度上是未知的.最近,一些研究报道了QRICH1的从头变异,并且这些变异与以发育迟缓为特征的Ververi-Brady综合征有关,非特异性面部畸形,和低张力。
方法:全外显子组测序,临床检查,和功能实验进行,以确定我们的病人的病因。
结果:这里,我们又增加了一个严重生长迟缓的病人,房间隔缺损,说话含糊不清。全外显子组测序鉴定了QRICH1基因中的一种新的截短变体(MN_017730.3:c.1788dupC,p.Tyr597Leufs*9)。此外,功能实验证实了遗传变异的影响。
结论:我们的发现扩展了QRICH1在发育障碍中的变异谱,并为整个外显子组测序在Ververi-Brady综合征中的应用提供了证据。
QRICH1 encodes the glutamine-rich protein 1, which contains one caspase activation recruitment domain and is likely to be involved in apoptosis and inflammation. However, the function of the
QRICH1 gene was largely unknown. Recently, several studies have reported de novo variants in
QRICH1, and the variants have been associated with Ververi-Brady syndrome characterized by developmental delay, nonspecific facial dysmorphism, and hypotonia.
Whole exome sequencing, clinical examinations, and functional experiments were performed to identify the etiology of our patient.
Here, we added another patient with severe growth retardation, atrial septal defect, and slurred speech. Whole exome sequencing identified a novel truncation variant in the
QRICH1 gene (MN_017730.3: c.1788dupC, p.Tyr597Leufs*9). Furthermore, the functional experiments confirmed the effect of genetic variation.
Our findings expand the
QRICH1 variant spectrum in developmental disorders and provide evidence for the application of whole exome sequencing in Ververi-Brady syndrome.