Clinical Report: An Uncommon Stop-Gained MYZAP Mutation Linked to AVSD
Overview
This case study identifies a novel homozygous stop-gain variant in the MYZAP gene associated with atrioventricular septal defects (AVSD) in an Arabian family.
Background
Atrioventricular septal defects (AVSDs) are significant congenital heart anomalies often linked to trisomy 21, with an incidence of 4 to 5 per 10,000 live births. The identification of genetic variants associated with AVSD is important for understanding its pathophysiology.
Data Highlights
Whole-exome sequencing revealed a novel homozygous stop-gain variant in the MYZAP gene (NM_001018100.5:c.229C > T; p.Arg77Ter) in two affected siblings, with segregation analysis confirming heterozygous carriage in the father.
Key Findings
A novel homozygous stop-gain variant in MYZAP was identified in two siblings with AVSD.
The variant meets ACMG criteria for likely pathogenicity and is extremely rare in population databases.
The family presented with a spectrum of AVSD phenotypes, including complete AVSD and isolated cleft of the anterior mitral leaflet.
MYZAP is primarily associated with cardiomyopathy but may also play a role in congenital cardiac malformations.
Further functional studies are needed to validate the association of MYZAP with AVSD.
Clinical Implications
Understanding the genetic basis of AVSD can aid in management strategies for affected families.
Conclusion
This case study presents a novel MYZAP variant associated with AVSD, warranting further investigation.
by Zaher Zaher, Gaser Abdelmohsen, Saud Bahaidarah, Faris Baamer, Angham Abdulrhman Abdulkareem, Abdulmajeed F. Alrefaei, Muhammad Imran Naseer, Muhammad Abu-Elmagd
