ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components
| Autor: | Rohrbach, Marianne, Spencer, Helen L, Porter, Louise F, Burkitt-Wright, Emma M M, Bürer, Céline, Janecke, Andreas, Bakshi, Madhura, Sillence, David, Al-Hussain, Hailah, Baumgartner, Matthias, Steinmann, Beat, Black, Graeme C M, Manson, Forbes D C, Giunta, Cecilia |
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| Přispěvatelé: | University of Zurich, Giunta, Cecilia |
| Rok vydání: | 2013 |
| Předmět: |
Joint Instability
1303 Biochemistry Adolescent Genotype Endocrinology Diabetes and Metabolism DNA Mutational Analysis 610 Medicine & health Keratoconus Biochemistry Article Genetic heterogeneity Endocrinology 1311 Genetics 1312 Molecular Biology Genetics Humans Eye Abnormalities Child Molecular Biology Brittle cornea Exons Extracellular Matrix 1310 Endocrinology DNA-Binding Proteins PRDM5 and ZNF469 2712 Endocrinology Diabetes and Metabolism Single exon gene Gene Expression Regulation 10036 Medical Clinic Child Preschool 10076 Center for Integrative Human Physiology Mutation Skin Abnormalities 570 Life sciences biology Ehlers-Danlos Syndrome Female Keratoglobus Transcription Factors |
| Zdroj: | Molecular Genetics and Metabolism |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2013.04.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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