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

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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 12 q 21 .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 .