Unraveling Genetic Factors in Cleft Lip and Palate Among Japanese Patients: A Two Decade Effort

Watanabe A

Published on: 2023-12-14

Abstract

Objective

The development of cleft lip and palate (CL/P) has been studied around the world, but no single gene for cleft lip and palate has yet been identified. There are racial differences in the development of this disease, and its pathogenesis in the Japanese may have a complex pathomechanism. This two-decade study project, initiated in 2003, aimed to investigate the genetic underpinnings and potential racial variations contributing to the pathogenesis of cleft lip and palate in Japanese subjects.

Design

The study projects employed Sanger sequencing for mutation analysis, single nucleotide polymorphism (SNP) association analysis, Transmission Disequilibrium Test (TDT) through a case-control study, and GWAS, next-generation sequencing.

Setting

Participants

The study encompassed various Japanese and Vietnamese populations and analyzed candidate genes known for their links to cleft lip and palate (e.g. RYK, EPHB2, EPHB3, TGF-B3, DLX3, PAX9, CLPTM1, TBX10, PVRL1, TBX22, IRF6, WNT5A, WNT9B, TP63, MSX1, TFAP2A, DLX4, MN1).

Interventions

Methods included mutation analysis, SNPs association analysis, Genome-wide association analysis (GWAS), and next-generation sequencing to uncover novel genetic variants.

Main Outcome Measure(s): The primary outcomes included the identification of impactful missense mutations, novel SNPs, and potential genetic variants associated with cleft lip and palate in Japanese participants.

Results

Significant findings included impactful missense mutations, novel SNPs, and regions of interest in GWAS.

Conclusion

The study advanced our understanding of genetic factors linked to cleft lip and palate in Japanese subjects but did not yield a definitive pathogenesis explanation. It underscored the role of racial variations. Further research using long-read sequencers is needed to explore epigenomic factors and rare variants, deepening our grasp of the condition and its genetic intricacies.