PVR/CD155 Ala67Thr Mutation and Cleft Lip/Palate.

Area of Science:

• Genetics
• Developmental Biology
• Craniofacial Research

Background:

• The 19q13 chromosomal locus is implicated in the etiology of cleft lip and palate (CLP). Previous studies, including our own, have identified associations within this region.
• Identifying specific etiological variants is crucial for understanding CLP pathogenesis and developing targeted interventions.

Purpose of the Study:

• To fine-map the 19q13 locus and identify genetic variants responsible for cleft lip and palate.
• To investigate the role of the PVR/CD155 gene and its Ala67Thr mutation in CLP.
• To assess the expression of PVR/CD155 in human saliva and its potential interaction with environmental factors.

Main Methods:

• Fine-mapping of the 19q13 interval (between D19S714 and D19S433) using linkage and association analyses in a cohort of 2739 individuals with CLP.
• Genotyping performed using TaqMan chemistry.
• Mutation analysis of PVR/CD155 Ala67Thr and assessment of its penetrance.
• Investigation of PVR/CD155 expression in human whole saliva.

Main Results:

• Association between markers in the PVR/CD155 gene and cleft lip and palate confirmed.
• The PVR/CD155 Ala67Thr mutation exhibits very low penetrance, estimated between 1% and 5%.
• PVR/CD155 expression was not detected in adult human whole saliva.
• Evidence suggests PVR/CD155 may interact with maternal infection to increase susceptibility to cleft lip.

Conclusions:

• Markers within the PVR/CD155 gene are significantly associated with cleft lip and palate.
• The low penetrance of the Ala67Thr mutation indicates it is unlikely to be the sole cause of CLP.
• PVR/CD155's role in CLP may involve interactions with environmental factors, such as maternal infections, particularly for non-syndromic cleft lip.