PAX7nucleotide variants and the risk of non‐syndromic orofacial clefts in the Polish population

Abstract

Objective The etiology of non‐syndromic cleft lip with or without cleft palate (nsCL/P) is multifactorial, heterogeneous, and still not completely understood. The aim of the present study was to examine the associations between common and rare PAX7 nucleotide variants and the risk of this common congenital anomaly in a Polish population. Subjects and methods Eight top nsCL/P‐associated PAX7 variants identified in our cleft genome‐wide association study (GWAS) were selected for replication analysis in an independent group of patients and controls (n = 247 and n = 445, respectively). In addition, mutation screening of the PAX7 protein‐coding region was conducted. Results Analysis of the pooled data from the GWAS and replication study confirmed that common PAX7 nucleotide variants are significantly associated with the increased risk of nsCL/P. The strongest individual variant was rs1339062 (c.586 + 15617T > C) with a p‐value = 2.47E−05 (OR = 1.4, 95%CI: 1.20–1.64). Sequencing analysis identified a novel synonymous PAX7 substitution (c.87G > A, p.Val29Val) in a single patient with nsCLP. This transition located in the early exonic position was predicted to disrupt potential splice enhancer elements. Conclusion Our study confirmed that PAX7 is a strong candidate gene for nsCL/P. Nucleotide variants of this gene contribute to the etiology of nsCL/P in the homogenous Polish population.

DeepFace: Deep-learning-based framework to contextualize orofacial-cleft-related variants during human embryonic craniofacial development

“… 57 , 58 Several SNPs have been reported to increase the risk of nonsyndromic CL/P. 59 , 60 Our finding thus supported the utilities of the DeepFace model; however, further experiment validation of the regulatory roles of these two SNPs will be warranted. We further discuss their roles below.…”

Maternal Transmission of the PAX7 Single Nucleotide Polymorphisms among Indian Cleft Trios

“…24 A multiethnic genome-wide meta-analysis of the rs9439714 showed a significant association with nonsyndromic orofacial clefts. 32,33 The rs1339062 was strongly associated with NSCL/P (p-value ¼ 2.47E À 05, OR ¼ 1.4) in the Polish population, 34 whereas in an Asian and European trio, the SNP rs1339062 showed no significance. 35 Guo et al found no significance for rs6695765 and rs742071 in a case-control study on nonsyndromic orofacial clefts from northern China.…”

Identification of microRNAs and gene regulatory networks in cleft lip common in humans and mice

“…In humans, SNPs or mutations in the FGFR1 gene are associated with non-syndromic CL/P ( 84 , 85 ). PAX7, a TF containing a paired box domain, an octapeptide, and a paired-type homeodomain, plays roles in craniofacial development ( 86 ), and PAX7 nucleotide variants are associated with non-syndromic CL/P ( 87 ). SUMO1, an ubiquitin-like protein, plays roles in various cellular processes, such as nuclear transport, transcriptional regulation, and apoptosis, through sumoylation of many genes.…”