Identification of Causative Variants Contributing to Nonsyndromic Orofacial Clefts Using Whole-Exome Sequencing in a Saudi Family.

Objectives

Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial malformations observed across the globe. They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and palate. To identify the potential candidate genes contributing to polygenic diseases such as NSOFC, linkage analyses, genome-wide association studies, and genomic rearrangements can be used. Genomic analyses, based on massively parallel next-generation sequencing technologies, play a vital role in deciphering the genetic bases of NSOFCs. Materials and

Methods

In this study, whole exome sequencing was employed to detect genes that likely contributed to the NSOFC phenotype in a consanguineous Saudi family.

Results

The exome analysis revealed NRP1 (rs35320960) as one potential candidate gene that is involved in bone differentiation. The RPL27A gene (rs199996172), which plays a crucial role in ribosome biogenesis, also passed all filters to serve as a candidate gene for NSOFC in this family. Rare variants are situated within the 5' UTR of these two genes.

Conclusion

The study suggests that rare variants in NRP1 and RPL27A may be associated with NSOFC disease etiology.