VSX1: a gene for posterior polymorphous dystrophy and keratoconus

Elise Héon; Alex Greenberg; Kelly K Kopp; David Rootman; Andrea L Vincent; Gail Billingsley; Megan Priston; Kimberley M Dorval; Robert L Chow; Roderick R McInnes; Godfrey Heathcote; Carol Westall; John E Sutphin; Elena Semina; Rod Bremner; Edwin M Stone

doi:10.1093/hmg/11.9.1029

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VSX1: a gene for posterior polymorphous dystrophy and keratoconus

Journal article

Peer reviewed

VSX1: a gene for posterior polymorphous dystrophy and keratoconus

Elise Héon, Alex Greenberg, Kelly K Kopp, David Rootman, Andrea L Vincent, Gail Billingsley, Megan Priston, Kimberley M Dorval, Robert L Chow, Roderick R McInnes, …

Human molecular genetics, Vol.11(9), pp.1029-1036

05/01/2002

DOI: 10.1093/hmg/11.9.1029

PMID: 11978762

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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.

Mutation

Retina - metabolism

Homeodomain Proteins - metabolism

Humans

Molecular Sequence Data

Infant

Male

Keratoconus - metabolism

Fuchs' Endothelial Dystrophy - pathology

Polymorphism, Single-Stranded Conformational

DNA Mutational Analysis

Keratoconus - genetics

Aged, 80 and over

Adult

Female

Keratoconus - pathology

Eye Proteins - genetics

Child

Fuchs' Endothelial Dystrophy - metabolism

Electroretinography

Amino Acid Sequence

Fuchs' Endothelial Dystrophy - genetics

Reverse Transcriptase Polymerase Chain Reaction

Homeodomain Proteins - genetics

Sequence Homology, Amino Acid

Eye Proteins - metabolism

Pedigree

Aged

Retina - pathology

Details

Title: Subtitle: VSX1: a gene for posterior polymorphous dystrophy and keratoconus
Creators: Elise Héon - Cellular and Molecular Division, Toronto Western Research Institute, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. eheon@uhnres.utoronto.ca
Alex Greenberg
Kelly K Kopp
David Rootman
Andrea L Vincent - Hospital for Sick Children
Gail Billingsley
Megan Priston
Kimberley M Dorval
Robert L Chow
Roderick R McInnes
Godfrey Heathcote
Carol Westall
John E Sutphin
Elena Semina
Rod Bremner
Edwin M Stone
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.11(9), pp.1029-1036
DOI: 10.1093/hmg/11.9.1029
PMID: 11978762
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Language: English
Date published: 05/01/2002
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980014802771

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