Confirmation and refinement of the heterozygous deletion of the small leucine-rich proteoglycans associated with posterior amorphous corneal dystrophy. (4th July 2018)

• Record Type: Journal Article
• Authors: Cervantes, Aleck E.; Gee, Katherine M.; Whiting, Martha F.; Frausto, Ricardo F.; Aldave, Anthony J.
• Is Part Of: Ophthalmic genetics. Volume 39:Number 4(2018)
• Page Start: 419
• Page End: 424
• Publication Date: 2018-07-04
• Subjects: CNV -- copy number variation -- OCT -- optical coherence tomography -- PACD -- posterior amorphous corneal dystrophy -- SLRPs -- small leucine-rich proteoglycans; Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.1080/13816810.2018.1459736
• Languages: English
• ISSNs: 1381-6810

Abstract

ABSTRACT: Purpose : To present the clinical and cytogenetic features of a previously unreported family with posterior amorphous corneal dystrophy (PACD) associated with a heterozygous deletion of the small leucine-rich proteoglycan (SRLP) genes on chromosome 12. Methods : Clinical characterization was performed using slit lamp biomicroscopic and optical coherence tomography (OCT) imaging. Genomic DNA was collected from affected and unaffected family members, and a cytogenomic array was used to identify copy number variations (CNV) present in the PACD locus. Results : Three members of a Guatemalan family presented with clinical characteristics consistent with PACD: bilateral posterior stromal lamellar opacification, decreased corneal curvature, and iridocorneal adhesions. OCT imaging demonstrated decreased corneal thickness and hyperreflectivity of the posterior third of the corneal stroma. CNV analysis confirmed the presumed clinical diagnosis of PACD by revealing a 0.304 Mb heterozygous deletion in the PACD locus on chromosome 12 that included the four SLRP genes ( KERA, LUM, DCN, and EPYC ) deleted in each of the PACD families in which CNV analysis has been reported. Conclusions : This is the first report of the OCT appearance of PACD and the second confirmation of a heterozygous deletion of chromosome 12q21.33 as the cause of PACD, highlighting the utility of array-based cytogenomics to confirm the suspected clinical diagnosis of PACD. As the smallest previously reported pathogenic deletion was 0.701 Mb, the 0.304-Mb deletion we report is the smallest identified to date and reduces the size of the PACD locus to 0.275 Mb.