title: VSX1: a gene for posterior polymorphous dystrophy and keratoconus.
abstract: We identified mutations in the VSX1 homeobox gene for two distinct inherited corneal dystrophies; posterior polymorphous dystrophy (PPD) and keratoconus. One of the mutation (R166W) responsible for keratoconus altered the homeodomain and impaired DNA binding. Two other sequence changes (L159M and G160D) were associated with keratoconus and PPD, respectively, and involved a region adjacent to the homeodomain. The G160D substitution, and a fourth defect affecting the highly conserved CVC domain (P247R), occurred in a child with very severe PPD who required a corneal transplant at 3 months of age. In this family, relatives with the G160D change alone had mild to moderate PPD, while P247R alone caused no corneal abnormalities. However, with either the G160D or P247R mutation, electroretinography detected abnormal function of the inner retina, where VSX1 is expressed. These data define the molecular basis of two important corneal dystrophies and reveal the importance of the CVC domain in the human retina.
authors.affiliation: Cellular and Molecular Division, Toronto Western Research Institute, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. eheon@uhnres.utoronto.ca
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
authors.forename: Alex
authors.initials: A
authors.lastname: Greenberg
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Kopp
authors.forename: David
authors.initials: D
authors.lastname: Rootman
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Vincent
authors.forename: Gail
authors.initials: G
authors.lastname: Billingsley
authors.forename: Megan
authors.initials: M
authors.lastname: Priston
authors.forename: Kimberley M
authors.initials: KM
authors.lastname: Dorval
authors.forename: Robert L
authors.initials: RL
authors.lastname: Chow
authors.forename: Roderick R
authors.initials: RR
authors.lastname: McInnes
authors.forename: Godfrey
authors.initials: G
authors.lastname: Heathcote
authors.forename: Carol
authors.initials: C
authors.lastname: Westall
authors.forename: John E
authors.initials: JE
authors.lastname: Sutphin
authors.forename: Elena
authors.initials: E
authors.lastname: Semina
authors.forename: Rod
authors.initials: R
authors.lastname: Bremner
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007640:Keratoconus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012160:Retina / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C491583:VSX1 protein, human