Unraveling the genetic architecture of non-syndromic cleft lip and palate in association with dental agenesis: genomic mapping

• Grant number: 24/18301-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Lucimara Teixeira das Neves
• Grantee: Ana Laura Herrera Farha
• Host Institution: Hospital de Reabilitação de Anomalias Craniofaciais (HRAC). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Non-syndromic cleft lip and palate (NSCLP) is a congenital craniofacial anomaly that affects more than 130,000 babies worldwide each year. The global rehabilitation protocol requires a series of procedures across multiple areas, creating social, emotional, and financial burdens that impact the quality of life for individuals and their families, as well as the public healthcare system. Among the numerous phenotypes associated with NSCLP, dental agenesis (DA) stands out. The coexistence of these two phenotypes characterizes a condition of multiple anomalies with a complex multifactorial etiology, involving the interaction of genetic, environmental, and epigenetic factors. Epidemiological data and the close embryological relationship between NSCLP and DA support the hypothesis that these phenotypes share a similar genetic background. To date, no study has analyzed this association as a specific condition through Whole Genome Sequencing (WGS). Therefore, there is a gap in understanding the genetic etiology of this association, which is highly prevalent in clinical practice and increases the complexity of rehabilitation. WGS has been effective in discovering new genes related to complex conditions, expanding the understanding of potential genetic susceptibility factors. The aim of this project is to unravel the genetic architecture of NSCLP associated with DA by investigating and identifying genetic variants involved in the etiology of this condition using WGS in a family-based study, with and without recurrence, in a Brazilian population. This study aims to make a significant contribution to the field by identifying genetic predisposition markers, offering new insights into understanding the molecular pathways and specific signaling cascades in the occurrence of these two phenotypes, and establishing a polygenic risk score that could be used in risk analysis and management. This would provide support for more accurate genetic counseling and guide new preventive strategies in public policies to reduce the clinical impact of these conditions.