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Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant
FL. Braddock, JC. Gardner, N. Bhattacharyya, B. Sanchez-Pintado, M. Costa, C. Zarouchlioti, A. Szabo, P. Lišková, ME. Cheetham, RD. Young, C. Thaung, AE. Davidson, SJ. Tuft, AJ. Hardcastle
Language English Country England, Great Britain
Document type Journal Article
Grant support
Wellcome Trust - United Kingdom
NLK
Free Medical Journals
from 2009
PubMed Central
from 2009 to 1 year ago
Europe PubMed Central
from 2009 to 1 year ago
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1998-01-01
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
- MeSH
- Corneal Dystrophies, Hereditary * genetics pathology MeSH
- Decorin genetics metabolism MeSH
- Adult MeSH
- Extracellular Matrix Proteins * genetics MeSH
- Heterozygote MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation, Missense * MeSH
- Calcium-Binding Proteins * genetics MeSH
- Pedigree * MeSH
- Aged MeSH
- Corneal Stroma pathology metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits. Whole genome sequence data were generated for four affected individuals. No rare variants (MAF < 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G > A; p.(Glu112Lys), which is predicted to be damaging, segregated with disease. SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. Interestingly, SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Therefore, we performed immunohistochemistry to compare SPARCL1 and decorin localisation in corneal tissue from an affected family member and an unaffected control. Strikingly, the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. In summary, we describe a novel autosomal dominant corneal stromal dystrophy associated with a missense variant in SPARCL1, extending the phenotypic and genetic heterogeneity of inherited corneal disease.
Department of Corneal and External Eye Disease Moorfields Eye Hospital London UK
Structural Biophysics Group School of Optometry and Vision Sciences Cardiff University Cardiff UK
UCL Institute of Ophthalmology University College London London UK
References provided by Crossref.org
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