Journal
MOLECULAR GENETICS AND METABOLISM
Volume 109, Issue 3, Pages 289-295Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2013.04.014
Keywords
Brittle cornea; Keratoconus; Keratoglobus; PRDM5 and ZNF469; Single exon gene; Genetic heterogeneity
Funding
- UBS Donation
- Gottfried und Julia Bangerter-Rhyner-Stiftung
- Action Medical Research in Manchester
- Wellcome Trust
- UK National Institute for Health Research
- Fight for Sight
- Action Medical Research [1967] Funding Source: researchfish
- National Institute for Health Research [BRF-2011-015, ACF-2007-06-011] Funding Source: researchfish
- National Institutes of Health Research (NIHR) [BRF-2011-015] Funding Source: National Institutes of Health Research (NIHR)
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Brittle cornea syndrome (BCS; MIM 229200) is an autosomal recessive generalized connective tissue disorder caused by mutations in ZNF469 and PRDM5. It is characterized by extreme thinning and fragility of the cornea that may rupture in the absence of significant trauma leading to blindness. Keratoconus or keratoglobus, high myopia, blue sclerae, hyperelasticity of the skin without excessive fragility, and hypermobility of the small joints are additional features of BCS. Transcriptional regulation of extracellular matrix components, particularly of fibrillar collagens, by PRDM5 and ZNF469 suggests that they might be part of the same pathway, the disruption of which is likely to cause the features of BCS. In the present study, we have performed molecular analysis of a cohort of 23 BCS affected patients on both ZNF469 and PRDM5, including those who were clinically reported previously [1]; the clinical description of three additional patients is reported in detail. We identified either homozygous or compound heterozygous mutations in ZNF469 in 18 patients while, 4 were found to be homozygous for PRDM5 mutations. In one single patient a mutation in neither ZNF469 nor PRDM5 was identified. Furthermore, we report the 12 novel ZNF469 variants identified in our patient cohort, and show evidence that ZNF469 is a single exon rather than a two exon gene. (C) 2013 Elsevier Inc. All rights reserved.
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