RESUMO
Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, â¼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10(-2)). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10(-5); ORallelic = 2.46 [95% CI 1.6-3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10(-9)). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO.
Assuntos
Fissura Palatina/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Fases de Leitura Aberta , Fatores de Transcrição/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Alelos , Estudos de Casos e Controles , Fenda Labial/diagnóstico , Fenda Labial/genética , Fissura Palatina/diagnóstico , Cistos/diagnóstico , Cistos/genética , Humanos , Lábio/anormalidades , Mutação , Polimorfismo de Nucleotídeo Único , Grupos Raciais/genéticaRESUMO
OBJECTIVES: The premature loss of primary teeth is a potential risk factor for poor arch length development. Adequate arch length is important to the progression of the permanent teeth. Poor arch length can lead to crowding, ectopic eruption, or impaction of these teeth. This study is designed to assess the prevalence of premature loss of primary teeth in the 5-10-year-old age group. MATERIALS AND METHODS: The study group included 185 children, that is, 91 boys and 94 girls. The dental examination was conducted by an experienced examiner under sufficient artificial light. Data including patient age and missing teeth were collected. Descriptive statistics were applied for data analysis, and from the results, Chi-square tests were used at a level of significance of 5% (P < 0.05). RESULTS: We observed a 40.54% prevalence of premature loss of primary teeth with no statistically significant difference between genders. The lower left primary second molar was the most commonly absent tooth in the dental arch (13.5%). CONCLUSION: The status of premature loss of primary teeth was high in the study group. Implementation of efficient educational and preventive programs to promote oral health would help children maintain a healthy primary dentition and eventually prevent the disturbances in the future development of normal occlusion. Early detection and management of the space problems associated with the early loss of primary teeth would help in reducing malocclusion problems.