Department of Oral and Maxillofacial Surgery, affiliated Dongguan Hospital, Southern Medical University (Dongguan people's Hospital), Dongguan, China.
Department of Pediatric Endocrinology and Metabolism, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital of Sichuan University, Chengdu, China.
Mol Genet Genomic Med. 2023 Aug;11(8):e2227. doi: 10.1002/mgg3.2227. Epub 2023 Jun 18.
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.
QRICH1 编码富含谷氨酰胺的蛋白 1，它包含一个半胱氨酸天冬氨酸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，有几项研究报道了 QRICH1 中的从头变异，这些变异与以发育迟缓、非特异性面部畸形和张力减退为特征的 Ververi-Brady 综合征有关。
对我们的患者进行全外显子组测序、临床检查和功能实验，以确定病因。
在这里，我们增加了另一名患有严重生长迟缓、房间隔缺损和言语不清的患者。全外显子组测序在 QRICH1 基因中发现了一个新的截断变异（MN_017730.3：c.1788dupC，p.Tyr597Leufs*9）。此外，功能实验证实了遗传变异的影响。
我们的发现扩展了发育障碍中 QRICH1 变异谱，并为全外显子组测序在 Ververi-Brady 综合征中的应用提供了证据。
