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The article focuses on identifying a novel splicing mutation in the Ectodysplasin A (EDA) gene within a hypohidrotic ectodermal dysplasia (HED) pedigree, exploring the molecular pathogenesis of HED through genetic testing technologies. Topics covered include the characterization of HED, involvement of specific genes like EDA, and the identification of various mutation types leading to HED, emphasizing the significance of this novel splicing mutation in the EDA gene within a Chinese family.

Objectives: Non‐syndromic cleft palate only (NSCPO) is a common congenital deformity with complex etiologies. GRHL3, FAF1, and KCNJ2 have been reported to be involved in the pathogenesis of NSCPO. Up till now, there have been no replication studies based on large Han Chinese. Therefore, this study aimed to investigate associations between GRHL3, FAF1, KCNJ2, and NSCPO sub‐phenotypes patients in Han Chinese. Materials and Methods: Firstly, we selected 2 SNPs based on previous literatures: FAF1 (rs3827730) and GRHL3 (rs41268753). Also, we selected 8 tagSNPs in GRHL3 (rs557811, rs609352, rs10903078, rs6659209, rs12401714, rs12568599, rs3887581, rs12024148) and 2 tagSNPs in KCNJ2 (rs75855040 and rs236514). Afterward, we evaluated these SNPs among 1668 NSCPO patients and 1811 normal controls from Han Chinese. Following data were analyzed by PLINK and Haploview program. Results: Association analysis under additive model showed that allele A at rs12568599 in GRHL3 gene is significantly associated with NSCPO (p = 0.0034, OR = 1.38 and 95%CI: 1.11–1.72) and its sub‐phenotype incomplete cleft palate (ICP) (p = 0.0039, OR = 1.4 and 95%CI: 1.11–1.75), and it could increase the risk of both NSCPO and ICP. Conclusions: This study firstly found that rs12568599 in GRHL3 is associated with NSCPO and ICP in Han Chinese, indicating that sub‐phenotypes of NSCPO have different etiologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder, and it results from both of the genetic modifiers and environmental factors, with genetic modifiers contributes to it more than environmental factors. GWASs made great progress in identifying the candidate genes for NSCL/P, but the findings need to be replicated in other populations. In this study, we selected eleven SNPs from recent GWASs and GWAS meta-analysis to investigate their associations among 308 NSCL/P trios (134 non-syndromic cleft lip only (NSCLO) trios and 174 non-syndromic cleft lip with cleft palate (NSCLP) trios) from Han Chinese population. All SNPs were genotyped using SNPscan method and analyzed the data with FBAT, PLINK, and R package. Allelic TDT analysis showed that allele A at rs12543318 was associated with NSCLO trios (P = .0032, OR = 0.57, 95% CI: 0.39-0.83), and parent-of-origin effect analysis indicated that allele A at rs12543318 was significantly maternally undertransmitted among NSCLO (P = .0046), which implied the potential influence of genomic imprinting; global TDT further confirmed this association. Individual genotypic TDT showed homozygote C/C at rs12543318 was overtransmitted among NSCLO (Z = 3.79, P = .00015) and NSCL/P groups (Z = 3.83, P = .00013), which indicated that it could increase the risk to have cleft babies. Our findings indicated that rs12543318 was associated with NSCLO from Western Han Chinese population, which will give new scientific evidence for later researches in the etiology of NSOCs. [ABSTRACT FROM AUTHOR]

Objective: Genome‐wide association studies (GWAS) found NTN1, NOG and the region between CREBBP and ADCY9 were risks to non‐syndromic cleft lip with or without cleft palate (NSCL/P). However, the association of single nucleotide polymorphisms (SNPs) in these genes with NSCL/P in Western China is unknown. Subjects and Methods: We selected seven SNPs in NTN1, NOG and between CREBBP and ADCY9, and then performed transmission disequilibrium test (TDT), parent‐of‐origin effect and sliding window haplotype analysis to test the associations among 302 NSCL/P case–parent trios from Western Han Chinese. Results: We found allele G at rs4791774 in NTN1 was significantly overtransmitted among non‐syndromic cleft lip only (NSCLO) (p = 0.0067, OR = 1.79, 95% CI: 1.17–2.74); rs4791774 and rs9915089 tightly linked with each other among NSCL/P (D′ = 0.87, r2 = 0.67) and haplotypes carrying the risk allele G at rs4791774 were always found to be overtransmitted from parents to cases. Motif analysis indicated that allele G at rs4791774 could greatly alter the affinity of Myc_disc7, so allele G at rs4791774 in NTN1 might modulate C‐MYC transcription to participate in the aetiology of NSCLO. Conclusions: Our study suggested allele G at rs4791774 in NTN1 gene is risk of NSCLO, which could greatly increase the risk to have a baby with cleft. [ABSTRACT FROM AUTHOR]

Background: Non-syndromic orofacial clefts (NSOCs) are complex disease involving genetic triggers, environmental factors, and their interplay. Recent studies demonstrated that EYA1, a member of eye absent gene family, might contribute to NSOCs.Methods: We investigated three single nucleotide polymorphisms (SNPs) and eight environmental factors (multivitamin, folic acid and calcium supplementation history, maternal alcohol consumption, common cold history, maternal smoking and environmental tobacco smoke in the first trimester, and paternal smoking in the 3 months before pregnancy) among 294 case-parent trios and 183 individual controls in western Han Chinese to evaluate the relationship between EYA1, environmental factors, and NSOCs. To be better known the gene's role in the etiology of NSOCs, we performed statistical analysis in different aspects including the linkage disequilibrium test, transmission disequilibrium test, haplotype analysis, multiple logistic regression analysis, and conditional logistic regression analysis.Results: Allele C at rs3779748 showed an over-transmission in NSCL/P trios (P = 0.03), and genotype A/A at rs10094908 was under-transmitted among NSCL/P trios (P = 0.03), whereas over-transmitted among NSCPO trios (P = 0.02). The haplotype GC of rs10094908-rs3779748 was over-transmitted among NSCL/P trios (P = 0.05) and NSCPO trios (P = 0.05), respectively. Maternal common cold history, environmental tobacco smoke, and maternal alcohol consumption during the first trimester of pregnancy were risk factors for NSOCs, while calcium supplementation during the first trimester showed a protective effect. No evidence of interactions between EYA1 and environmental factors was found.Conclusions: These results revealed an association between EYA1, some environmental factors, and NSOCs in western Han Chinese. [ABSTRACT FROM AUTHOR]

Background Non-syndromic orofacial clefts (NSOC) are the most common craniofacial birth defects and are considered as complex and multifactorial diseases involving the interplay of genetic predisposition and environmental exposures. Recent studies demonstrated that EYA1, a member of eye absent gene family, might contribute to the development of orofacial clefts. This study aimed to evaluate the association between EYA1 gene polymorphism and NSOC in western Chinese population. Method Two single-nucleotide polymorphisms, rs13260349 and rs2380716, were investigated among 199 case-parent trios, and the linkage disequilibrium (LD) test, transmission disequilibrium test, family based association test, and haplotype analysis were performed. Results Weak evidence of LD was found between these markers (D' = 0.573, r2 = 0.218); allel C and genotype C/C at rs13260349 showed an overtransmission in CL/P; haplotype T-T (rs13260349-rs2380716) displayed an association with NSOC and CL/P. Conclusions The results showed evidence of weak association between the two SNPs of EYA1 (rs13260349 and rs2380716) and NSOC. [ABSTRACT FROM AUTHOR]