Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12.
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.
Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Michelle J
MJ
Kim
Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Ricardo F
RF
Frausto
The Central Pennsylvania Eye Institute, Hershey, Pennsylvania, United States of America.
George O D
GO
Rosenwasser
Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Tina
T
Bui
Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Derek J
DJ
Le
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.
Edwin M
EM
Stone
Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Anthony J
AJ
Aldave
D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism*; D058575:Decorin / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics; D000071234:Lumican; D008297:Male; D010375:Pedigree; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D000071232:Small Leucine-Rich Proteoglycans
D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; C119499:EPYC protein, human; C490948:KERA protein, human; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D000071232:Small Leucine-Rich Proteoglycans; D007632:Keratan Sulfate