Screening of Transforming Growth Factor Beta 3 and Jagged2 Genes in the Malay Population with Nonsyndromic Cleft Lip with or without Cleft Palate

• Published in: The Cleft palate-craniofacial journal 2015-07, Vol.52 (4), p.88-94
• Main Authors: Ghazali, Norliana, Rahman, Normastura Abd, Kannan, Thirumulu Ponnuraj, Jaafar, Saidi
• Format: Article
• Language: English
• Subjects: Chromatography, High Pressure Liquid; Cleft Lip - genetics; Cleft Palate - genetics; Confidence intervals; Cross-Sectional Studies; Dentistry; Deoxyribonucleic acid; DNA; Female; Genes; Growth factors; Humans; Introns; Jagged-2 Protein - genetics; Malaysia; Male; Mutation; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Population; Prevalence; Software; Studies; Transforming Growth Factor beta3 - genetics
• ISSN: 1055-6656; 1545-1569
• DOI: 10.1597/14-024

Objective To determine the prevalence of mutations in transforming growth factor beta 3 (TGFβ3) and Jagged2 genes and their association with nonsyndromic cleft lip with or without cleft palate (CL±P) patients. Design Cross-sectional study on nonsyndromic CL±P and noncleft patients. Setting Reconstructive clinic and outpatient dental clinic, Hospital Universiti Sains Malaysia. Patients Blood samples of 96 nonsyndromic CL±P and 96 noncleft subjects. Main Outcome Measure Prevalence and association of mutations in TGFβ3 and Jagged2 genes with nonsyndromic CL±P. Results Most of the nonsyndromic CL±P patients (53.1%) had left unilateral CLP. There were slightly more females (56.6%) compared with males. The prevalence of the mutations in the TGFβ3 gene was 17.7% (95% confidence interval [CI]: 9.5, 24.5) and in the Jagged2 gene was 12.5% (95% CI: 5.5, 18.5), which was higher compared with the noncleft group. For the TGFβ3 gene, there was no mutation in the coding region in either of the groups. All variants were single nucleotide polymorphisms located within the intronic flanking region. Two variants were identified (g.15812T>G and g.15966A>G) in both nonsyndromic CL±P and noncleft patients. However, the association was not significant (P > .05). Three variants (g.19779C>T, g.19547G>A, and g.19712C>T) were identified in the Jagged2 gene among nonsyndromic CL±P and noncleft patients. Only g.19712C>T showed a significant association with nonsyndromic CL±P patients (P = .039). Conclusion g.19712C>T might play a crucial role in the development of cleft lip and palate. To the best of our knowledge, this is the first report of the mutation found within intron 13 of the Jagged2 gene among nonsyndromic CL±P Malay patients.