Genetics in Heterotaxy: A Case Series and Literature Review on DNAH9, PKD1L1, MMP21, and GDF1.
Thi Bich Tuyen Ho, Alicia Coudert, Thi Thuy Hang Do et al.
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Case in brief
This case series involved seven children and fetuses with heterotaxy (HTX) from France and Vietnam, characterized by complex congenital heart defects and extracardiac abnormalities. Through trio-based whole-exome and whole-genome sequencing, seven variants in four genes (DNAH9, PKD1L1, MMP21, GDF1) were identified, revealing significant phenotypic heterogeneity and strong genotype-phenotype correlations, particularly linking MMP21 and GDF1 variants to severe conotruncal malformations.
What made this case unusual
The identification of two unreported variants expands the known mutational spectrum associated with laterality defects, contributing to the understanding of HTX.
Diagnostic / clinical pearl
Next-generation sequencing (NGS) significantly enhances the diagnostic yield in heterotaxy cases, facilitating earlier and more personalized clinical management.
Why it matters
This study emphasizes the importance of integrating advanced genomic analyses with clinical data to refine the understanding of genotype-phenotype correlations in congenital heart defects.