Abstract
Background 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. ARHGAP29, 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. Methods 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. Results We identified a novel heterozygous missense variant of ARHGAP29 (c.2615C > T, p.A872V) in a Chinese pedigree with NSCL/P. Conclusion We detected the disease-causing variant in this NSCL/P family. Our identification expands the genetic spectrum of ARHGAP29 and contributes to novel approaches to the genetic diagnosis and counseling of CL/P families.
Highlights
Cleft lip with or without cleft palate (CL/P) is one of the most prevalent human birth defects, with a worldwide incidence of 1 in 700-1000 live births [1]
According to whether patients have other organ malformations, CL/P is divided into syndromic CL/P (SCL/P) and nonsyndromic CL/P (NSCL/P)
NSCL/P is thought to have a complex etiology, with genetic factors acting in concert with environmental effects, which leads to variable phenotypes and incomplete penetrance [3, 9]
Summary
Cleft lip with or without cleft palate (CL/P) is one of the most prevalent human birth defects, with a worldwide incidence of 1 in 700-1000 live births [1]. With the increasing availability of genome-wide association studies (GWAS) and wholeexome sequencing (WES), many genes have been identified as NSCL/P causative genes, including CTNND1, PLEKHA5, PLEKHA7, CDH1, and ARHGAP29 [3, 10, 11]. 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. The present study investigated a Chinese family with NSCL/P and explored potential pathogenic variants using whole-exome sequencing (WES). We identified a novel heterozygous missense variant of ARHGAP29 (c.2615C > T, p.A872V) in a Chinese pedigree with NSCL/P. Our identification expands the genetic spectrum of ARHGAP29 and contributes to novel approaches to the genetic diagnosis and counseling of CL/P families
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