Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population, a preliminary report

Objective: Nonsyndromic oral clefts are common craniofacial anomalies classified into two subgroups: cleft lip with or without cleft palate and isolated cleft palate. Nonsyndromic oral clefts are multifactorial diseases, with both genetic and environmental factors involved in their pathogenesis. The inhibitory neurotransmitter, γ-aminobutyric acid plays a role in normal embryonic, and particularly facial, development and γ-aminobutyric acid receptor type A β-3 subunit (GABRB3) knockout mice have been shown to have cleft palate. The GABRB3 gene is therefore a strong candidate gene for nonsyndromic oral clefts. We investigated here whether genetic variations of the GABRB3 gene affect the risk for nonsyndromic oral clefts. Method: In this case-control study, a total of 178 Japanese patients with cleft lip with or without cleft palate and 374 unrelated controls were recruited and were genotyped for six single nucleotide polymorphisms and a dinucleotide repeat marker of the GABRB3 gene. Results: None of the single nucleotide polymorphisms showed complete linkage disequilibrium with other single nucleotide polymorphisms. In a case-control association study with the six-locus haplotype of the gene, TGTGCT haplotype frequency in patients with cleft lip with or without cleft palate was significantly higher than in the controls (corrected p value = .029). None of the alleles of the dinucleotide repeat marker showed significant association with cleft lip with or without cleft palate. Conclusions: Our data suggest that the GABRB3 gene is involved in the pathogenesis of cleft lip with or without cleft palate in the Japanese population.

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Association Between PAX9 Single-Nucleotide Polymorphisms and Nonsyndromic Cleft Lip With or Without Cleft Palate

Journal of Craniofacial Surgery ◽

10.1097/scs.0b013e31824e27c7 ◽

2012 ◽

Vol 23 (5) ◽

pp. 1262-1266 ◽

Cited By ~ 14

Author(s):

Jin Kyung Lee ◽

Ji Wan Park ◽

Young Ho Kim ◽

Seung-Hak Baek

Keyword(s):

Single Nucleotide Polymorphisms ◽

Cleft Palate ◽

Cleft Lip ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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A Mutation in RYK is a Genetic Factor for Nonsyndromic Cleft Lip and Palate

The Cleft Palate-Craniofacial Journal ◽

10.1597/04-145.1 ◽

2006 ◽

Vol 43 (3) ◽

pp. 310-316 ◽

Cited By ~ 18

Author(s):

Akira Watanabe ◽

Sadanori Akita ◽

Nguyen Thi Duc Tin ◽

Nagato Natsume ◽

Yoko Nakano ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Cleft Palate ◽

Missense Mutation ◽

Cleft Lip ◽

Case Control Study ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Transmission Disequilibrium ◽

Control Study

Objective The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate. Setting Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms. Results A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined. Conclusion The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.

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