Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12

Michelle J Kim; Ricardo F Frausto; George O D Rosenwasser; Tina Bui; Derek J Le; Edwin M Stone; Anthony J Aldave

doi:10.1371/journal.pone.0095037

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Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12

Journal article

Open access

Peer reviewed

Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12

Michelle J Kim, Ricardo F Frausto, George O D Rosenwasser, Tina Bui, Derek J Le, Edwin M Stone and Anthony J Aldave

PloS one, Vol.9(4), pp.e95037-e95037

2014

DOI: 10.1371/journal.pone.0095037

PMCID: PMC3997350

PMID: 24759697

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Abstract

Posterior amorphous corneal dystrophy (PACD) is a rare, autosomal dominant disorder affecting the cornea and iris. Next-generation sequencing of the previously identified PACD linkage interval on chromosome 12q21.33 failed to yield a pathogenic mutation. However, array-based copy number analysis and qPCR were used to detect a hemizygous deletion in the PACD linkage interval containing 4 genes encoding small leucine-rich proteoglycans (SLRPs): KERA, LUM, DCN, and EPYC. Two other unrelated families with PACD also demonstrated deletion of these SLRPs, which play important roles in collagen fibrillogenesis and matrix assembly. Given that these genes are essential to the maintenance of corneal clarity and the observation that knockout murine models display corneal phenotypic similarities to PACD, we provide convincing evidence that PACD is associated with haploinsufficiency of these SLRPs.

Chondroitin Sulfate Proteoglycans - genetics

Humans

Corneal Dystrophies, Hereditary - genetics

Proteoglycans - metabolism

Male

Corneal Dystrophies, Hereditary - metabolism

Keratan Sulfate - genetics

Small Leucine-Rich Proteoglycans

Pedigree

Female

High-Throughput Nucleotide Sequencing

Lumican

Genetic Linkage - genetics

Chromosomes, Human, Pair 12 - genetics

Decorin - genetics

Proteoglycans - genetics

Sequence Deletion - genetics

Details

Title: Subtitle: Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12
Creators: Michelle J Kim - Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
Ricardo F Frausto - Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
George O D Rosenwasser - The Central Pennsylvania Eye Institute, Hershey, Pennsylvania, United States of America
Tina Bui - Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
Derek J Le - University of California, Los Angeles
Edwin M Stone - Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America
Anthony J Aldave - Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(4), pp.e95037-e95037
DOI: 10.1371/journal.pone.0095037
PMID: 24759697
PMCID: PMC3997350
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: R01 EY022082 / NEI NIH HHS
Language: English
Date published: 2014
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979955702771

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