Homozygous Mutations in PXDN Cause Congenital Cataract, Corneal Opacity, and Developmental Glaucoma

• Published in: American journal of human genetics Vol. 89; no. 3; pp. 464 - 473
• Main Authors: Khan, Kamron, Rudkin, Adam, Parry, David A., Burdon, Kathryn P., McKibbin, Martin, Logan, Clare V., Abdelhamed, Zakia I.A., Muecke, James S., Fernandez-Fuentes, Narcis, Laurie, Kate J., Shires, Mike, Fogarty, Rhys, Carr, Ian M., Poulter, James A., Morgan, Joanne E., Mohamed, Moin D., Jafri, Hussain, Raashid, Yasmin, Meng, Ngy, Piseth, Horm, Toomes, Carmel, Casson, Robert J., Taylor, Graham R., Hammerton, Michael, Sheridan, Eamonn, Johnson, Colin A., Inglehearn, Chris F., Craig, Jamie E., Ali, Manir
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 09.09.2011; Cell Press; Elsevier
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cataract - genetics; Cataract - pathology; Cornea - metabolism; Cornea - pathology; Corneal Opacity - genetics; Corneal Opacity - pathology; Enzymes; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Eye diseases; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic Predisposition to Disease - genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Glaucoma; Glaucoma - genetics; Glaucoma - pathology; Humans; Lens diseases; Medical genetics; Medical sciences; Mice; Microscopy, Fluorescence; Models, Molecular; Molecular and cellular biology; Molecular Sequence Data; Mutation; Mutation - genetics; Ophthalmology; Pedigree; Peroxidase - chemistry; Peroxidase - genetics; Peroxidase - metabolism; Peroxidasin; Proteins; Sequence Analysis, DNA; Human; Eye disease; Cataract; Lens disease; Congenital; Glaucoma (eye); Genetics; Mutation; Homozygosity; Corneal opacity; Anterior segment disease
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2011.08.005

Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.