Identification of Novel and Rare Gene Variants in Cleft Lip/Palate Patients From Kuwaiti Consanguineous Families by Exome Sequencing.

Abstract

The prevalence of Cleft Lip with or without Cleft Palate (CLP) varies by geography and ethnicity, particularly in consanguineous populations. This study aimed to identify gene variants contributing to the development of both syndromic (SCLP) and non-syndromic (NSCLP) forms of the condition in 20 consanguineous Kuwaiti families. We used exome sequencing and assessed the variants' predicted functional roles. Seven rare gene variants were identified across all cases, including one novel variant (LRRC32) in a syndromic case and three variants (SH3PXD2A, DUOX1, MSX2) in non-syndromic cases. These genes are predicted to be involved in cellular metabolism, differentiation, signaling, and regulatory mechanisms. Four genes (SH3PXD2A, DUOX1, MSX2, and ACACB) identified in the non-syndromic cases were found to have a significant association with co-expression of the transcription factor TP63. These findings provide a foundation for further investigation into the functional roles of these novel variants in the development of NSCLP, particularly DUOX1, which has not been previously reported in CLP.