A novel VSX1 mutation identified in an individual with keratoconus in India

Purpose To evaluate the possible role of the VSX1 gene in a group of patients from the Indian subcontinent with keratoconus. Methods Molecular analysis of 66 patients with a diagnosis of keratoconus, based on clinical examination and corneal topography, was carried out. DNA extraction from peripheral blood followed by Polymerase Chain Reaction (PCR) amplification of the VSX1 gene was performed. The entire coding region and the exon–intron junctions of the VSX1 gene were analyzed by direct sequencing. Results A novel change at c.525G>C, replacing amino acid glutamine at position 175 with histidine, was found in one affected individual. One of the previously reported SNPs (rs12480307) was found with equal frequency in both patients and controls. Conclusions This is the first report from the Indian subcontinent exploring the role of VSX1 in the causation of keratoconus. One novel mutation (Q175H) predicted to be a potentially damaging change was seen in an affected individual; this substantiates the importance of this gene but its precise role in disease causation needs further investigation.

[1]  G. Fishman,et al.  CRB1 gene mutations are associated with keratoconus in patients with leber congenital amaurosis. , 2009, Investigative ophthalmology & visual science.

[2]  C. Joo,et al.  VSX1 gene variants are associated with keratoconus in unrelated Korean patients , 2008, Journal of Human Genetics.

[3]  E. Cohen,et al.  Indications for Penetrating Keratoplasty and Associated Procedures, 2001–2005 , 2008, Eye & contact lens.

[4]  P. E. Dantas,et al.  [Trends in the indications for penetrating keratoplasty]. , 2008, Arquivos brasileiros de oftalmologia.

[5]  Y. Rabinowitz,et al.  Three VSX1 Gene Mutations, L159M, R166W, and H244R, Are Not Associated With Keratoconus , 2008, Cornea.

[6]  Haike Reznik Wolf,et al.  The D144E Substitution in the VSX1 Gene: A Non-pathogenic Variant or a Disease Causing Mutation? , 2008, Ophthalmic genetics.

[7]  R. Gwilliam,et al.  Molecular analysis of the VSX1 gene in familial keratoconus. , 2007, Molecular vision.

[8]  Y. Rabinowitz,et al.  No VSX1 gene mutations associated with keratoconus. , 2006, Investigative ophthalmology & visual science.

[9]  Terry Kim,et al.  Trends in the Indications for Penetrating Keratoplasty, 1980-2001 , 2005, Cornea.

[10]  K. Taylor,et al.  Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1 , 2005, Genetics in Medicine.

[11]  L. Zelante,et al.  VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation. , 2005, Investigative ophthalmology & visual science.

[12]  S. Deeb,et al.  Expression of Rinx/Vsx1 during postnatal eye development in cone-bipolar, differentiating ganglion, and lens fiber cells , 2005, Japanese Journal of Ophthalmology.

[13]  S. Claude,et al.  Efficience des critères vidéokératographiques quantitatifs dans l’analyse familiale de patients atteints de kératocône , 2004 .

[14]  A. Bird,et al.  The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. , 2004, Archives of ophthalmology.

[15]  J. Féher,et al.  A locus for autosomal dominant keratoconus maps to human chromosome 3p14–q13 , 2004, Journal of Medical Genetics.

[16]  B. Arnaud,et al.  [Accuracy of videokeratographic quantitative criteria for detection of keratoconus suspects in families with keratoconus]. , 2004, Journal francais d'ophtalmologie.

[17]  Y. Rabinowitz.  The genetics of keratoconus. , 2003, Ophthalmology clinics of North America.

[18]  D. Frazer,et al.  Familial keratoconus with cataract: linkage to the long arm of chromosome 15 and exclusion of candidate genes. , 2003, Investigative ophthalmology & visual science.

[19]  P. Sistonen,et al.  A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families. , 2002, Investigative ophthalmology & visual science.

[20]  R. Mcinnes,et al.  VSX1: a gene for posterior polymorphous dystrophy and keratoconus. , 2002, Human molecular genetics.

[21]  Janice M. Fullerton,et al.  Identity-by-descent approach to gene localisation in eight individuals affected by keratoconus from north-west Tasmania, Australia , 2002, Human Genetics.

[22]  E. Cohen,et al.  Indications for Penetrating Keratoplasty and Associated Procedures, 1996–2000 , 2002, Cornea.

[23]  C. McGhee,et al.  The genetics of keratoconus , 2001, Clinical & experimental ophthalmology.

[24]  S. Deeb,et al.  RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina. , 2000, Genomics.

[25]  S Rozen,et al.  Primer3 on the WWW for general users and for biologist programmers. , 2000, Methods in molecular biology.

[26]  T T McMahon,et al.  Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. , 1998, Investigative ophthalmology & visual science.

[27]  E. Puffenberger,et al.  Molecular Genetic Analysis in Autosomal Dominant Keratoconus , 1992, Cornea.