Spectrum of phenotype and genetic variants in a Suzhou cohort of fetuses with cleft lip and/or palate

Background Advances in genomic technologies, including chromosomal microarray (CMA) and whole-exome sequencing (WES), have provided tools to explore genetic factors of cleft lip and/or palate (CL/P). However, further investigation is warranted to identify the spectrum of phenotype and genetic variants in both syndromic and non-syndromic CL/P. Methods Fifty-seven patients with CL/P participated in this study, with 46 undergoing CMA analysis and 11 undergoing WES. Clinical data comprising demographic characteristics, clinical details, and genetic analysis results were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological significance of these genes. Results Demographic characteristics of samples undergoing CMA and WES were described. The frequency of associated malformations showed variations across different CL/P classifications, with congenital heart defects the most commonly reported. The majority of cases (81.25%) by CMA had no definitive genetic findings. In contrast, 65.45% of the cases by WES carried likely pathogenic/pathogenic (LP/P) variants or variants of uncertain significance (VUS). Additionally, functional enrichment analysis highlighted the significant involvement of genes associated with regulation of mesenchymal cell proliferation in CL/P pathogenesis. Conclusions This study underscores the significance of CMA and WES for the genetic diagnosis of CL/P, with CMA detecting known CNV related to disease and CNV in non-coding regions, as well as WES providing enhanced efficacy in single nucleotide variations. Involvement of causal genes in mesenchymal cell proliferation and other biological process presents promising therapeutic targets for the treatment of CL/P.