Abstract
BACKGROUND Non-syndromic cleft lip with cleft palate (NSCLP) is one of the most common congenital birth defects worldwide; it causes lifelong problems and imposes burdens on patients and their families. This study aimed to describe the genomic analysis and identification of de novo regulated endocrine-specific protein 18 (RESP18) rs2385404 and rs2385405 gene polymorphisms associated with NSCLP in a southern Chinese family and to improve prevention, treatment, and prognosis of NSCLP. MATERIAL AND METHODS We performed a genome-wide association study (GWAS) to investigate the association of NSCLP phenotype with gene mutation. We investigated a 5-persons NSCLP family to screen the genetic variation of Han nationality in southern Chinese. Whole-genome sequencing (WGS) was used to detect all candidate genetic variants, and whole-exome sequencing (WES) was implemented to further verify mutations. The Clinical Variation Data Base (ClinVar) was employed for screening gene mutations. Finally, Sanger sequencing was applied to verify gene variations. RESULTS The combined analysis of WGS, WES, and ClinVar showed that a total of 9 variation positions overlapped among the 3 study cohorts. Sanger sequencing verified Glu amino acid variation in 2 mutation sites (rs2385404, rs2385405) from the RESP18 gene, which caused abnormal RESP18 function and was associated with hereditary NSCLP. CONCLUSIONS The combined genomic results showed that 2 mutations (rs2385404 and rs2385405) of the RESP18 gene were related to NSCLP in the family. The RESP18 gene may play an important role in the etiology and pathogenesis of cleft lip and palate.