title: Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma.
abstract: 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.
authors: Leeds Institute of Molecular Medicine, UK.
authors: Kamron
authors: K
authors: Khan
authors: Adam
authors: A
authors: Rudkin
authors: David A
authors: DA
authors: Parry
authors: Kathryn P
authors: KP
authors: Burdon
authors: Martin
authors: M
authors: McKibbin
authors: Clare V
authors: CV
authors: Logan
authors: Zakia I A
authors: ZI
authors: Abdelhamed
authors: James S
authors: JS
authors: Muecke
authors: Narcis
authors: N
authors: Fernandez-Fuentes
authors: Kate J
authors: KJ
authors: Laurie
authors: Mike
authors: M
authors: Shires
authors: Rhys
authors: R
authors: Fogarty
authors: Ian M
authors: IM
authors: Carr
authors: James A
authors: JA
authors: Poulter
authors: Joanne E
authors: JE
authors: Morgan
authors: Moin D
authors: MD
authors: Mohamed
authors: Hussain
authors: H
authors: Jafri
authors: Yasmin
authors: Y
authors: Raashid
authors: Ngy
authors: N
authors: Meng
authors: Horm
authors: H
authors: Piseth
authors: Carmel
authors: C
authors: Toomes
authors: Robert J
authors: RJ
authors: Casson
authors: Graham R
authors: GR
authors: Taylor
authors: Michael
authors: M
authors: Hammerton
authors: Eamonn
authors: E
authors: Sheridan
authors: Colin A
authors: CA
authors: Johnson
authors: Chris F
authors: CF
authors: Inglehearn
authors: Jamie E
authors: JE
authors: Craig
authors: Manir
authors: M
authors: Ali
mesh_terms: D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003318:Corneal Opacity / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005901:Glaucoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D009195:Peroxidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000097423:Peroxidasin
chemical_list: D016326:Extracellular Matrix Proteins; D009195:Peroxidase; D000097423:Peroxidasin