The following new article has just been published in Orphanet Journal of Rare Diseases

Research

Bruch’s membrane abnormalities in PRDM5-related brittle cornea syndrome

Porter L, Gallego-Pinazo R, Keeling C, Kamieniorz M, Zoppi N, Colombi M, Giunta C, Bonshek R, Manson F, Black GOrphanet Journal of Rare Diseases 2015, 10 :145 (11 November 2015)

Abstract | Full Text | PDF

Research

Bruch’s membrane abnormalities in PRDM5-related brittle cornea syndrome

Louise F. Porter¹²³, Roberto Gallego-Pinazo⁴, Catherine L. Keeling⁵, Martyna Kamieniorz⁵,Nicoletta Zoppi⁶, Marina Colombi⁶, Cecilia Giunta⁷, Richard Bonshek²⁸, Forbes D. Manson¹ and Graeme C. Black¹⁹^*

*Corresponding author: Graeme C BlackGraeme.Black@manchester.ac.uk

Author Affiliations

¹Institute of Human Development, Centre for Genomic Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Saint Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK

²Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK

³Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK

⁴Department of Ophthalmology, Unit of Macula, University and Polytechnic Hospital La Fe, Valencia, Spain

⁵Histopathology, Central Manchester University Hospitals, NHS Foundation Trust, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK

⁶Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Brescia, Italy

⁷Division of Metabolism, Connective Tissue Unit, University Children’s Hospital and Children’s Research Centre, (CRC) Zurich, Switzerland

⁸Department of Histopathology, National Ophthalmic Pathology Service (NSOPS) Laboratory, Central Manchester University Hospitals, NHS Foundation Trust, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK

⁹Centre for Genomic Medicine, Central Manchester University Hospitals, NHS Foundation Trust, MAHSC, Saint Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK

For all author emails, please log on.

Orphanet Journal of Rare Diseases 2015, 10:145 doi:10.1186/s13023-015-0360-4

The electronic version of this article is the complete one and can be found online at:http://www.ojrd.com/content/10/1/145

Received:	27 March 2015
Accepted:	19 October 2015
Published:	11 November 2015

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

Background

Brittle cornea syndrome (BCS) is a rare, generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Recessive mutations in transcription factors ZNF469 and PRDM5 cause BCS. Both transcription factors are suggested to act on a common pathway regulating extracellular matrix genes, particularly fibrillar collagens. We identified bilateral myopic choroidal neovascularization as the presenting feature of BCS in a 26-year-old-woman carrying a novel PRDM5 mutation (p.Glu134*). We performed immunohistochemistry of anterior and posterior segment ocular tissues, as expression of PRDM5 in the eye has not been described, or the effects of PRDM5-associated disease on the retina, particularly the extracellular matrix composition of Bruch’s membrane.

Methods

Immunohistochemistry using antibodies against PRDM5, collagens type I, III, and IV was performed on the eyes of two unaffected controls and two patients (both with Δ9-14 PRDM5). Expression of collagens, integrins, tenascin and fibronectin in skin fibroblasts of a BCS patient with a novel p.Glu134* PRDM5 mutation was assessed using immunofluorescence.

Results

PRDM5 is expressed in the corneal epithelium and retina. We observe reduced expression of major components of Bruch’s membrane in the eyes of two BCS patients with a PRDM5 Δ9-14 mutation. Immunofluorescence performed on skin fibroblasts from a patient with p.Glu134* confirms the generalized nature of extracellular matrix abnormalities in BCS.

Conclusions

PDRM5-related disease is known to affect the cornea, skin and joints. Here we demonstrate, to the best of our knowledge for the first time, that PRDM5 localizes not only in the human cornea, but is also widely expressed in the retina. Our findings suggest that ECM abnormalities in PRDM5-associated disease are more widespread than previously reported.