Rare single-nucleotide variants in oculo-auriculo-vertebral spectrum (OAVS)

Area of Science:

• Genetics
• Developmental Biology
• Craniofacial Anomalies

Background:

• Oculo-auriculo-vertebral spectrum (OAVS) is a complex craniofacial disorder affecting first and second pharyngeal arch derivatives.
• Phenotype is heterogeneous, involving anomalies in mandibular, oral, and ear development.
• Genetic factors are implicated, but known pathogenic single-nucleotide variants (SNVs) are limited to the MYT1 gene.

Purpose of the Study:

• Investigate SNVs in candidate genes to uncover additional pathogenic mechanisms in OAVS.
• Expand the understanding of genetic underpinnings of this heterogeneous disorder.
• Identify novel genetic variants contributing to OAVS etiology.

Main Methods:

• Sequencing of coding and untranslated regions (UTR) of 10 candidate genes in 73 OAVS patients.
• Selection and in silico prediction of pathogenicity for rare SNVs.
• Validation of likely pathogenic variants via Sanger sequencing and heritability assessment.

Main Results:

• Four likely pathogenic variants were identified in heterozygous state across different patients.
• Two SNVs were found in the 5'UTR of YPEL1.
• One SNV each was identified in the 3'UTR of CRKL and OTX2.

Conclusions:

• This study identified variants in candidate genes associated with Oculo-auriculo-vertebral spectrum.
• The findings support the significant genetic heterogeneity of OAVS.
• Further research into candidate genes is crucial for understanding OAVS pathogenesis.