Susceptibility genes in the etiology of nonsyndromic cleft lip and palate anomalies
Introduction/Context/Diagnosis
Several susceptibility genes (AKA candidate genes) MTHFR, TGFA, IRF6, MSX1, TGFB3 and others have been found associated with nonsyndromic cleft lip with or without cleft palate (NCL/P), one of the most common birth defects around the world. Among these genes, Interferon Regulatory Factor 6 (IRF6), a member of the IRF family of transcription factors, known to play an important role in orofacial development, has been found associated with NCL/P. Several studies have established IRF6 mutations as a monogenic cause of syndromic cleft lip and palate, namely Van der Woude syndrome. In NCL/P, IRF6 may be part of a complex multifactorial etiology. Our objective is to conduct a pilot study to determine, if IRF6 gene variants are associated with NCL/P in Karaikal, India.
Methods/Treatment Plan
A case-control design (cases = 50; controls = 44) was chosen for this pilot study. The group of cases comprised 15 cases of bilateral nonsyndromic cleft lip and palate (NCLP), 15 cases of unilateral NCLP on the left side, and 15 cases of unilateral NCLP on the right side. The control group consisted of 22 males and 22 females from the same location. We included five additional cases with Van der Woude syndrome. DNA was isolated from dry blood blots on filter paper. IRF6 rs2235371 variant was analyzed using rtPCR and genotype proportions and allele frequencies were compared between cases and controls.
Results/Outcome
The mutated allele T of IRF6 rs2235371 variant was rare in our samples. Even slightly higher in controls compared to cases (cases: T=0.12, C=0.88; controls T=0.1364, C= 0.8636). There was no homozygote TT in cases and 2 were observed in control sample. In cases, 76% had the CC genotype, 24% had the CT genotype, while in controls, 77.3% had the CC genotype, 18.2% had the CT genotype, and 4.5% had the TT genotype. There was no statistically significant difference between genotype distributions, neither between allele frequencies of cases and controls. There are some interesting differences seen – like the highest frequency of T alleles in right side unilateral cases (T=0.1667), however again not significant. Our results warrant expansion of our study with a larger sample size.
Significance/Conclusions
There is no study exploring association of IRF6 variants with NCL/P in India. Results of this study suggest feasibility of our approach, and that association of the IRF6 gene variant with NCLP in India needs to be further clarified. Our study will continue analyzing IRF6 rs2235371 variant on a larger sample of cases and controls and also analyzing other IRF6 variants.
Location
University of the Pacific, Dugoni Dental School, San Francisco, CA
Format
Poster
Poster Session
1st and 2nd Year Student Research Presentations
Susceptibility genes in the etiology of nonsyndromic cleft lip and palate anomalies
University of the Pacific, Dugoni Dental School, San Francisco, CA
Several susceptibility genes (AKA candidate genes) MTHFR, TGFA, IRF6, MSX1, TGFB3 and others have been found associated with nonsyndromic cleft lip with or without cleft palate (NCL/P), one of the most common birth defects around the world. Among these genes, Interferon Regulatory Factor 6 (IRF6), a member of the IRF family of transcription factors, known to play an important role in orofacial development, has been found associated with NCL/P. Several studies have established IRF6 mutations as a monogenic cause of syndromic cleft lip and palate, namely Van der Woude syndrome. In NCL/P, IRF6 may be part of a complex multifactorial etiology. Our objective is to conduct a pilot study to determine, if IRF6 gene variants are associated with NCL/P in Karaikal, India.
