Molecular analysis of the VSX1 gene in familial keratoconus.
OBJECTIVE
To evaluate the role of the visual system homeobox gene 1 (VSX1) in the pathogenesis of familial keratoconus.


METHODS
Families with two or more individuals with keratoconus were recruited and their members examined. The coding region and intron-exon junctions of the VSX1 gene were sequenced in affected individuals. In cases where there were possible pathogenic changes, segregation within the pedigree was analyzed. Meta analysis of reports on an association of p.D144E change with keratoconus phenotype was performed.


RESULTS
Probands from a panel of 85 apparently unrelated keratoconus families were included. Eleven sequence variants were observed, including the previously reported c.432C>G (p.D144E) change and two novel intronic single nucleotide polymorphisms. However, these three changes did not cosegregate with the disease phenotype.


CONCLUSIONS
We excluded the c.432C>G sequence alteration as the direct cause of the disease. Lack of possibly pathogenic VSX1 sequence variants in the familial panel suggests that involvement of this gene in the pathogenesis of keratoconus is likely to be confined to a small number of pedigrees, at least in the population studied.
Liskova
Petra
P
Division of Molecular Genetics, Institute of Ophthalmology, UCL, London, UK. p.liskova@ucl.ac.uk
Ebenezer
Neil D
ND
Hysi
Pirro G
PG
Gwilliam
Rhian
R
El-Ashry
Mohamed F
MF
Moodaley
Lalitha C
LC
Hau
Scott
S
Twa
Michael
M
Tuft
Stephen J
SJ
Bhatacharya
Shomi S
SS
D000328:Adult; D001224:Aspartic Acid; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D018698:Glutamic Acid; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
D005136:Eye Proteins; D018398:Homeodomain Proteins; C491583:VSX1 protein, human; D001224:Aspartic Acid; D018698:Glutamic Acid