Objective:

To investigate the genetic basis of atrioventricular septal defects (AVSDs) in an Arabian family and identify potential pathogenic variants.

Approach:

• Family Assessment: Clinical evaluation of an Arabian family with a spectrum of AVSD phenotypes, including echocardiography and electrocardiography.
• Genetic Analysis: Whole-exome sequencing was performed on three family members to identify genetic variants associated with AVSD.

Key Findings:

• A novel homozygous stop-gain variant in the MYZAP gene (NM_001018100.5:c.229C > T; p.Arg77Ter) was identified in two affected siblings.
• Segregation analysis confirmed heterozygous carriage in the father and absence in the unaffected mother.
• The variant is extremely rare in population databases and meets ACMG criteria for likely pathogenicity.

Interpretation:

This report expands the phenotypic spectrum associated with MYZAP and suggests a potential role in cardiac septation.

Limitations:

• The study is limited to a single family, which may not represent broader population genetics.
• Further functional studies are required to validate the association between MYZAP and AVSD.

Conclusion:

This report expands the phenotypic spectrum associated with MYZAP.