No VSX1 gene mutations associated with keratoconus.
OBJECTIVE
To determine whether mutations of the VSX1 gene play a pathogenetic role in the development of keratoconus (KTCN).


METHODS
DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN.


RESULTS
Of the four previously identified presumed pathogenic mutations in the VSX1 gene (Leu17Pro, Asp144Glu, Leu159Met, and Arg166Trp), only Asp144Glu was identified in a single affected patient. Two novel single nucleotide polymorphisms (SNPs), both resulting in synonymous substitutions, were identified: c.53G>T (Ser6Ser) in four affected patients and c.209G>T (Pro58Pro) in two affected patients. Two previously reported SNPs were also identified: c.426C>A (Arg131Ser) in one affected patient and c.581A>G (Ala182Ala) in 51 of the 100 affected patients.


CONCLUSIONS
Only one of the presumed pathogenic mutations in the VSX1 gene, Asp144Glu, was identified in a single member of the cohort of affected patients. However, as previously demonstrated, Asp144Glu is a non-disease-causing polymorphism. The absence of pathogenic mutations in the VSX1 gene in a large number of unrelated KTCN patients indicates that other genetic factors are involved in the development of this disorder.
Aldave
Anthony J
AJ
Cornea Service, The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. aldave@jsei.ucla.edu
Yellore
Vivek S
VS
Salem
Andrew K
AK
Yoo
Gina L
GL
Rayner
Sylvia A
SA
Yang
Huiying
H
Tang
George Y
GY
Piconell
Yoana
Y
Rabinowitz
Yaron S
YS
D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007640:Keratoconus / Q000235:genetics* / Q000601:surgery; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
D005136:Eye Proteins; D018398:Homeodomain Proteins; C491583:VSX1 protein, human