Brittle Cornea Syndrome Panel

Brittle cornea syndrome (BCS) is a rare , generalized connective tissue disorder, which is characterized by keratoconus or keratoglobus, hyperelasticity of the skin without excessive fragility, and hypermobility of the joints, blue sclerae, with extreme corneal thinning and a high risk of corneal rupture following a minor trauma (Rohrbach et al. 2013; Porter et al. 2015).

So far, bi-allelic pathogenic variants in ZNF469 and PRDM5 are reported to cause autosomal recessive Brittle cornea syndrome. ZNF469 and PRDM5 are transcription factors that are suggested to act on a common pathway regulating extracellular matrix genes, particularly fibrillar collagens (Porter et al. 2015). So far ~ 25 causative variants (missense, nonsense and small deletions and duplications) in ZNF469 and over 10 causative variants in PRDM5 (missense, nonsense, splicing and small and gross deletions) have been reported (Human Gene Mutation Database).

See individual gene test descriptions for more information on molecular biology of gene products.

This panel provides full coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

A molecular screening of ZNF469 and PRDM5 in 23 Brittle cornea syndrome patients identified either homozygous or compound heterozygous causative variants in ZNF469 in 18 patients, and homozygous causative variants in PRDM5 in 4 patients (Rohrbach et al. 2013).