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PLXND1 – Persistent Truncus Arteriosus

Isolated persistent truncus arteriosus has been linked to autosomal recessive PLXND1 mutations. In a consanguineous family with two affected siblings (PMID:24254849), homozygosity mapping and whole exome sequencing identified a homozygous PLXND1 c.3895C>T (p.Arg1299Cys) variant segregating with disease and absent in controls. Segregation in a single pedigree provides Limited genetic evidence under ClinGen standards.

Functional studies demonstrate that the p.Arg1299Cys substitution disrupts the intracellular anchoring region of plexin-D1, as predicted by in silico modelling, and Plxnd1 knockout mice exhibit truncus arteriosus phenocopy, supporting a haploinsufficiency mechanism and providing Moderate functional evidence (PMID:24254849). Additional cases are required to escalate clinical validity. Key take-home: PLXND1 screening may aid molecular diagnosis in non-syndromic truncus arteriosus.

References

  • American Journal of Medical Genetics. Part A • 2013 • Isolated truncus arteriosus associated with a mutation in the plexin-D1 gene. PMID:24254849

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single consanguineous family with 2 affected individuals ([PMID:24254849]); segregation and functional concordance with murine knockout model

Genetic Evidence

Limited

One homozygous PLXND1 variant in a single pedigree with segregation data ([PMID:24254849])

Functional Evidence

Moderate

In silico structural modelling and Plxnd1 knockout mouse phenocopy truncate arteriosus ([PMID:24254849])