3 research outputs found
Linkage analysis in keratoconus: replication of locus 5q21.2 and identification of other suggestive Loci.
PURPOSE. Keratoconus (KC) is the most common indication for
corneal transplantation in the Western world, with etiologic
mechanisms still poorly understood. The disease prevalence in
the general population is approximately 1:2000, and familial
aggregation, together with increased familial risk, suggests important
genetic influences on its pathogenesis. To date, several
loci for familial keratoconus have been described, without the
identification of any responsible gene in the respective
mapped intervals. The aim of this study was to identify causative/
susceptibility genes for keratoconus.
METHODS. A total of 133 individuals (77 affected and 59 unaffected)
of 25 families from southern Italy were genotyped
using microsatellite markers and included in a genome-wide
scan. Nonparametric and parametric analysis using an affectedonly
strategy were calculated by using genetic algorithm software.
RESULTS. The chromosomal regions 5q32-q33, 5q21.2, 14q11.2,
15q2.32 exhibited the strongest evidence of linkage by nonparametric
analysis (NPL 3.22, 2.73, 2.62, and 2.32, respectively).
The regions 5q32-q33 and 14q11.2 were also supported
by multipoint parametric analysis, for which heterogeneity
LOD (HLOD) scores of 2.45 ( 0.54) and 2.09 ( 0.46),
respectively, were obtained under an affected-only dominant
model.
CONCLUSIONS. This study represents the first KC linkage replication
study on the chromosomal region 5q21.2 and reports
evidence of suggestive linkage in several regions for which
suggestive or significant linkage has been previously detected
in different populations. (Invest Ophthalmol Vis Sci. 2009;50:
1081–1086) DOI:10.1167/iovs.08-238
VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation.
PURPOSE:
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