Prevalence of non-syndromic orofacial clefts: based on 15,094,978 Chinese perinatal infants

Fan, Dazhi; Wu, Shuzhen; Liu, Li; Xia, Qing; Tian, Guo; Wang, Wen; Ye, Shaoxin; Wang, Limin; Rao, Jiaming; Yang, Xiao; Yu, Zhen; Xin, Lihong; Song, Li; Duan, Zhijian; Zhang, Tianchen; Wu, Song; Guo, Xiaoling; Liu, Zheng­ping

doi:10.18632/oncotarget.24238

Cited by 42 publications

(33 citation statements)

References 51 publications

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“…Asian and Native American ancestry populations generally exhibit the highest birth prevalence rates for nonsyndromic orofacial cleft (NSOFC), whereas European ancestry populations have intermediate prevalence rates, and African ancestry populations have the lowest prevalence rates [7]. The overall prevalence of NSOFC in China is 1.67 per 1,000 newborns, with rates for CPO (2.7), CLO (5.6) and CLP (8.2 per 10,000 newborns) [8].…”

Section: Introductionmentioning

confidence: 99%

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft

et al. 2019

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Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10−8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

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Section: Introductionmentioning

confidence: 99%

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft

et al. 2019

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“…CL/P is one of the most common developmental deformities with an incidence rate of 1.67‰ in China, of which approximately 70% cases are NSCL/P [ 15 ]. In NSCL/P cases, 80% are sporadic and 20% are familial cases [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Variant of ARHGAP29 in a Chinese Family with Nonsyndromic Cleft Lip and Palate

Tang

Xiao

Wang

et al. 2020

BioMed Research International

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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.

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“…Non‐syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects with a global incidence of 1 in 700–1,000 people (Dixon, Marazita, Beaty, & Murray, 2011), with Asians have the highest incidence, followed by Europeans and Africans are the lowest (Mossey, Little, Munger, Dixon, & Shaw, 2009). According to the latest epidemiological survey, the birth prevalence rate was 1.67‰ for NSCL/P, 0.56‰ for non‐syndromic cleft lip only (NSCLO), 0.82‰ for non‐syndromic cleft lip and palate (NSCLP), and 0.27‰ for non‐syndromic cleft palate only (NSCPO) in China (Fan et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

SNPs at TP63 gene was specifically associated with right‐side cleft lip in Han Chinese population

et al. 2020

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Objectives Non‐syndromic cleft lip with or without palate is one of the most common birth malformations. TP63 and GREM1 were recently reported to be associated with NSCL/P. However, there were few studies focused on their associations in non‐syndromic cleft lip only (NSCLO). Design Initial screening and replication in large cohorts were used to locate the susceptible SNPs of TP63 and GREM1. Firstly, variations were screened among 192 NSCLO cases by the Sanger sequencing. Then, we selected five associated SNPs in initial screening phase and replicated among 1,006 NSCLO cases and 1,823 normal controls. Results Initial chi‐square test showed that rs7653848, rs7624324, rs6790167, and rs1345186 in TP63 and rs2280738 in GREM1 achieved statistical significance (p < .05); the subsequent replication analysis showed that rs1345186 was specifically significant in right‐side cleft lip (RCL; p = .017, OR = 1.33, and 95% CI: 1.05–1.69). Conclusion This study firstly used the subphenotype of cleft lip samples to verify the association between TP63 and GREM1, which indicated that TP63 is a promising susceptible gene for RCL in Chinese population. And further confirmed the different etiology in the right‐sided cleft lip, left‐sided cleft lip, and bilateral cleft lip of NSCLO. This will give new reference for the future research and genetic counseling.

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Prevalence of non-syndromic orofacial clefts: based on 15,094,978 Chinese perinatal infants

Cited by 42 publications

References 51 publications

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft

Identification of a Novel Variant of ARHGAP29 in a Chinese Family with Nonsyndromic Cleft Lip and Palate

SNPs at TP63 gene was specifically associated with right‐side cleft lip in Han Chinese population

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