Department of Prosthodontics, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China.
Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Biomed Res Int. 2020 Oct 23;2020:8790531. doi: 10.1155/2020/8790531. eCollection 2020.
Cleft lip with or without cleft palate (CL/P) is the most common facial birth defect, with a worldwide incidence of 1 in 700-1000 live births. CL/P can be divided into syndromic CL/P (SCL/P) and nonsyndromic CL/P (NSCL/P). Genetic factors are an important component to the etiology of NSCL/P. , one of the NSCL/P disease-causing genes, mediates the cyclical regulation of small GTP binding proteins such as RhoA and plays an essential role in cellular shape, proliferation, and craniofacial development.
The present study investigated a Chinese family with NSCL/P and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatic analysis and prediction of variant pathogenicity. Cosegregation was subsequently conducted.
We identified a novel heterozygous missense variant of (c.2615C > T, p.A872V) in a Chinese pedigree with NSCL/P.
We detected the disease-causing variant in this NSCL/P family. Our identification expands the genetic spectrum of and contributes to novel approaches to the genetic diagnosis and counseling of CL/P families.
唇裂伴或不伴腭裂（CL/P）是最常见的面部出生缺陷，全球发病率为每 700-1000 例活产儿中有 1 例。CL/P 可分为综合征性 CL/P（SCL/P）和非综合征性 CL/P（NSCL/P）。遗传因素是 NSCL/P 病因学的重要组成部分。 是 NSCL/P 的致病基因之一，介导小 GTP 结合蛋白（如 RhoA）的周期性调节，在细胞形态、增殖和颅面发育中发挥重要作用。
本研究通过全外显子组测序（WES）对一个具有 NSCL/P 的中国家系进行了研究，并探讨了潜在的致病变异。通过生物信息学分析和变异致病性预测对变异进行筛选和过滤。随后进行共分离分析。
我们在一个具有 NSCL/P 的中国家系中发现了一个新的杂合错义变异 （c.2615C>T，p.A872V）。
我们在这个 NSCL/P 家系中检测到了致病变异。我们的发现扩展了 的遗传谱，为 CL/P 家系的遗传诊断和咨询提供了新的方法。
