Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)
2015 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 4, 463-473 p.Article in journal (Refereed) Published
Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.
Place, publisher, year, edition, pages
John Wiley & Sons, 2015. Vol. 36, no 4, 463-473 p.
COL17A1, BP180, cornea dystrophy, ERED, ddPCR
IdentifiersURN: urn:nbn:se:umu:diva-103155DOI: 10.1002/humu.22764ISI: 000352304200011PubMedID: 25676728OAI: oai:DiVA.org:umu-103155DiVA: diva2:815161
Contract grant sponsors: Umeå University and Västerbotten County Council, Research and Development Foundation sponsored by Västerbotten County Council, Cronqvists Stiftelse (administered by The Swedish Society of Medicine); Ögonfonden, Stiftelsen KMA; the National Swedish Research Council (521-2013-2612); National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology; Moorfields Special Trustees; Moorfields Eye Charity; the Lanvern foundation.2015-05-292015-05-182015-12-01Bibliographically approved