Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10484179" target="_blank" >RIV/00216208:11110/24:10484179 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/24:10484179

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=iP10gwL81p" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=iP10gwL81p</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41431-024-01687-8" target="_blank" >10.1038/s41431-024-01687-8</a>

Result language

angličtina

Original language name

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant

Original language description

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 &lt; 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G &gt; 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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30101 - Human genetics

Project

<a href="/en/project/NW24-06-00083" target="_blank" >NW24-06-00083: Ultra-rare diseases with an ocular phenotype: optimization of diagnostics and management powered by advanced genomic analyses, artificial intelligence and 3D facial digital phenotyping</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Human Genetics

ISSN

1018-4813

e-ISSN

1476-5438

Volume of the periodical

32

Issue of the periodical within the volume

12

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

1583-1589

UT code for WoS article

001295719900001

EID of the result in the Scopus database

2-s2.0-85201607649