VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation.
OBJECTIVE
Keratoconus is a noninflammatory corneal disorder that is clinically and genetically heterogeneous. Mutations in the VSX1 (visual system homeobox 1) gene have been identified for two distinct, inherited corneal dystrophies: posterior polymorphous corneal dystrophy and keratoconus. To evaluate the possible role of the VSX1 gene in a series of Italian patients, 80 keratoconus-affected subjects were screened for mutations.


METHODS
The diagnosis of keratoconus was made on the basis of clinical examination and corneal topography. The whole coding region and the exon-intron junctions of the VSX1 gene were analyzed by direct sequencing.


RESULTS
Three already-described changes, D144E, G160D, and P247R, and a novel L17P mutation were found in 7 of 80 unrelated patients (8.7%). Two undescribed intronic polymorphisms are also reported.


CONCLUSIONS
Mutational analysis of the VSX1 gene in a series of Italian patients revealed one novel mutation and confirmed an important role played by this gene in a significant proportion of patients affected by keratoconus, when it is inherited as an autosomal dominant trait with variable expressivity and incomplete penetrance.
Bisceglia
Luigi
L
Medical Genetics Service and Ophthalmology Department, IRCCS-CSS Hospital, San Giovanni Rotondo (Fg), Italy.
Ciaschetti
Marilena
M
De Bonis
Patrizia
P
Campo
Pablo Alberto Perafan
PA
Pizzicoli
Costantina
C
Scala
Costanza
C
Grifa
Michele
M
Ciavarella
Pio
P
Delle Noci
Nicola
N
Vaira
Filippo
F
Macaluso
Claudio
C
Zelante
Leopoldo
L
D000293:Adolescent; D000328:Adult; D002648:Child; D019781:Corneal Topography; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007558:Italy; D007640:Keratoconus / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D005136:Eye Proteins; D018398:Homeodomain Proteins; C491583:VSX1 protein, human