Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations

Lennon, Christen J.; Birkeland, Andrew C.; Nuñez, José Arturo Pacheco; Su, Gloria H.; Lanzano, Patricia; Guzman, Edwin R.; Celis, Katrina; Eisig, Sidney B.; Hoffman, David C.; Rendon, Maria Teresa Guerra; Ostos, Henry; Chung, Wendy K.; Haddad, Joseph

doi:10.1002/lary.23394

Cited by 38 publications

(37 citation statements)

References 24 publications

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“…Similar to studies in patients of European and Middle-South American descents (Nikopensius et al, 2011;Lennon et al, 2012), our results support a role for the FOXE1 in the development of CPO in the Thai population.…”

Section: Discussionsupporting

confidence: 89%

FOXE1 mutations in Thai patients with oral clefts

et al. 2013

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Summary Non-syndromic oral clefts comprising cleft lip with and without cleft palate (CL/P) and cleft palate only (CPO) are common birth defects worldwide. Their aetiology involves both environmental and genetic factors. FOXE1 has previously been reported to be associated with oral clefts in some populations. Here, we investigate whether mutations in FOXE1 play a part in the formation of oral cleft in a Thai population. We first performed PCR-RFLP to genotype a previously reported associated polymorphism, c.-1204C > G (rs111846096), in our cohort. No association was found. In addition, two unrelated unaffected controls were found to be homozygous GG, indicating that homozygous GG at this c.-1204 position was not sufficient for the development of oral clefts. We then sequenced the entire coding region of FOXE1 in 458 unrelated individuals (146 CPOs, 108 CL/Ps and 204 Thai controls). Five different non-synonymous variants, c.274G > T (p.D92Y), c.569C > G (p.P190R), c.569C > T (p.P190L), c.664C > T (p.R222C) and c.1090G > A (p.G364S), were identified in CPOs and one, c.572C > G (p.P191R), in CL/P. All these six variants were in heterozygous state, each identified in one patient, and absent in 204 controls. Except the p.P190R, which was previously reported, the other five variants were novel. Our study identifies probable susceptibility variants of FOXE1 for oral clefts in the Thai population.

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Section: Discussionsupporting

confidence: 89%

FOXE1 mutations in Thai patients with oral clefts

et al. 2013

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“…The most strongly associated SNPs were replicated in independent populations [Beaty et al , 2010; Lennon et al, 2012; Pan et al , 2011; Yildirim et al, 2012], which also showed a stronger signal in Asian families than in European ones. Mutations in ABCA4 cause several autosomal recessive retinal diseases [Tsybovsky et al , 2010].…”

Section: Nonsyndromic Orofacial Cleftsmentioning

confidence: 84%

“…Several markers on chromosome 20q12 near MAFB achieved genome-wide significance in the GENEVA Cleft Consortium GWAS in European and Asian populations, although the signal was much stronger in Asians [Beaty et al , 2010]. Several independent studies using diverse populations have replicated this association [Beaty et al, 2010; Lennon et al , 2012; Pan et al, 2011]. Sequencing of the single MAFB exon identified a missense mutation, H131Q (rs121912307), present in 3.5% of Filipinos with CL/P but only 0.7% of controls (p<0.0001).…”

Section: Nonsyndromic Orofacial Cleftsmentioning

confidence: 99%

Genetics of cleft lip and cleft palate

Leslie¹,

Marazita²

2013

American J of Med Genetics Pt C

376

355

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Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in individuals with these birth defects and their family members: from subclinical phenotypes to associated syndromic features that is mirrored by the many genes that contribute to the etiology of these disorders. Identification of these genes and loci has been the result of decades of research using multiple genetic approaches. Significant progress has been made recently due to advances in sequencing and genotyping technologies, primarily through the use of whole exome sequencing and genome-wide association studies. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies.

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“…In a Polish population, rs227731 polymorphism increased the risk of NSCL/P when analyzed under a dominant model (Mostowska et al, ). The presence of the C risk allele of rs227731 was also significantly associated with NSCL/P in a population from Honduras (Lennon et al, ). The recent genome meta‐analyses confirmed the association of rs227731 (Ludwig et al, ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

Aquino

Messetti

Hoshi

et al. 2014

Birth Defects Research

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Background: Although genome‐wide association studies have identified several susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations around the world, the role of most loci is unknown in the highly heterogeneous Brazilian population. Methods: To determine the association of 7 markers that showed genome‐wide significant association in Brazilians with NSCL/P, we conducted a structured association study conditioned upon the individual ancestry proportions to evaluate markers at 1p36 (rs742071), 2p21 (rs7590268), 3p11.1 (rs7632427), 8q21.3 (rs12543318), 13q31.1 (rs8001641), 15q22.2 (rs1873147), and 17q22 (rs227731) in 505 patients with NSCL/P and 594 healthy controls recruited from 2 different geographical regions of Brazil. The polymorphisms were genotyped by TaqMan 5′‐exonuclease allelic discrimination assay, and each sample was independently typed for 40 biallelic short insertion/deletion markers to characterize the genomic ancestry. Results: After Bonferroni correction for multiple tests, significant associations with NSCL/P were observed for rs742071, rs1873147, and rs227731. However, the frequency of the risk alleles varied between the geographical regions, according to the proportions of European and African genomic ancestry. The group enriched by European ancestry showed significant association with rs227731 (p = 0.001), whereas the group with high African ancestry was significantly associated with rs1873147 polymorphism (p = 0.005). The significant association with rs742071 was only detected in the combined sample (p = 0.005). Conclusion: The findings of the present study revealed the associations of 1p36 (rs742071), 15q22 (rs1873147), and 17p22 (rs227731) with NSCL/P in the Brazilian population, and further confirmed that the genetic heterogeneity of NSCL/P may be related to the different ethnic background of the affected individuals. Birth Defects Research (Part A) 100:36–42, 2014. © 2013 Wiley Periodicals, Inc.

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Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations

Abstract: This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations.

Cited by 38 publications

References 24 publications

FOXE1 mutations in Thai patients with oral clefts

FOXE1 mutations in Thai patients with oral clefts

Genetics of cleft lip and cleft palate

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

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