Characterization of a Familial Goldenhar Syndrome Case Using Whole-Exome Sequencing

Area of Science:

• Genetics
• Epigenetics
• Rare Diseases

Background:

• Goldenhar syndrome (oculo-auriculo-vertebral spectrum, OAVS) is a rare congenital disorder with significant phenotypic variability.
• Its genetic etiology is largely unexplored despite being a common craniofacial malformation.

Purpose of the Study:

• To identify genetic variants and epigenetic modifications contributing to Goldenhar syndrome.
• To investigate the molecular etiology in a Lebanese family with affected individuals.

Main Methods:

• Whole-exome sequencing was performed on a nuclear family.
• Complementary DNA methylation and gene ontology analyses were conducted.

Main Results:

• A shared missense variant in MID1 was identified, but causality was inconclusive.
• A de novo mutation in FBXW11 and a frameshift alteration in NDUFAF8 were found, potentially linked to phenotypes.
• DNA methylation analysis revealed hypomethylation in ZC3H3, suggesting epigenetic involvement.

Conclusions:

• Goldenhar syndrome exhibits genetic and epigenetic complexity.
• The study provides new molecular insights into the disorder's etiology.
• Challenges in variant interpretation for rare familial disorders were highlighted.