PRDM5 – Axenfeld-Rieger Syndrome

Axenfeld-Rieger syndrome is an autosomal dominant anterior segment dysgenesis characterized by iris malformations and early-onset glaucoma. While pathogenic variants in PITX2 and FOXC1 explain most cases, recent data implicate PRDM5 in ARS. In a three-generation family, whole-exome sequencing identified a novel heterozygous missense variant, c.877A>G (p.Lys293Glu), that segregated with disease and was absent from population controls (PMID:26489929).

The Lys293 residue is evolutionarily conserved and in silico tools predict a deleterious effect. Although PRDM5’s role in epigenetic regulation of extracellular matrix genes has been demonstrated in brittle cornea syndrome fibroblasts and retinal tissue, no functional assays have yet addressed its impact in ARS (PMID:26395458). Consequently, the genetic support remains limited to a single family and further studies are required to establish pathogenicity and mechanism. Key take-home: PRDM5 should be included in ARS diagnostic panels, but current evidence is preliminary.

References

• Neurogenetics • 2016 • Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld-Rieger syndrome. PMID:26489929
• Human molecular genetics • 2015 • A role for repressive complexes and H3K9 di-methylation in PRDM5-associated brittle cornea syndrome. PMID:26395458

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