Identification of Causative Variants Contributing to Nonsyndromic Orofacial Clefts Using Whole-Exome Sequencing in a Saudi Family.
PMID 33121284 | DOI 10.1089/gtmb.2019.0233 · Genetic testing and molecular biomarkers · 2020 · View on PubMed ↗
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | NRP1 | “Results: The exome analysis revealed NRP1 (rs35320960) as one potential candidate gene that is involved in bone differentiation.” | 0.98 | hgnc_dict_v1 |
| gene | RPL27A | “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.” | 0.98 | hgnc_dict_v1 |
| phenotype | cleft lip and palate | “They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and palate.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Identification of Causative Variants Contributing to Nonsyndromic Orofacial Clefts Using Whole-Exome Sequencing in a Saudi Family. 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.” | 0.95 | saudi_context_rules_v1 |
| variant | rs35320960 | “Results: The exome analysis revealed NRP1 (rs35320960) as one potential candidate gene that is involved in bone differentiation.” | 0.90 | hgvs_regex_v1 |
| variant | rs199996172 | “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.” | 0.90 | hgvs_regex_v1 |