Purchase this article with an account.
Abdul Hameed, Shagufta Khaliq, Muhammed Ismail, Khalid Anwar, Neil D. Ebenezer, Tim Jordan, S. Qasim Mehdi, Annette M. Payne, Shomi S. Bhattacharya; A Novel Locus for Leber Congenital Amaurosis (LCA4) with Anterior Keratoconus Mapping to Chromosome 17p13. Invest. Ophthalmol. Vis. Sci. 2000;41(3):629-633.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. A two-generation consanguineous Pakistani family with autosomal
recessive Leber congenital amaurosis (LCA, MIM 204,000) and keratoconus
was identified. All affected individuals have bilateral keratoconus and
congenital pigmentary retinopathy. The goal of this study was to link
the disease phenotype in this family.
methods. Genomic DNA was amplified across the polymorphic microsatellite poly-CA
regions identified by markers. Polymerase chain reaction (PCR) products
were separated by nondenaturing polyacrylamide gel electrophoresis.
Alleles were assigned to individuals, which allowed calculation of
LOD scores using the Cyrillic and MLINK software program. The
retinal guanylate cyclase (RETGC-1, GDB symbol GUC2D) and pigment
epithelium-derived factor (PEDF) genes were analyzed by
heteroduplex analysis and direct sequencing for mutations in diseased
results. Based on a whole genome linkage analysis the first locus for
this combined phenotype has been mapped to chromosome 17p13. Linkage
analysis gave a two point LOD score of 3.21 for marker D17S829.
Surrounding this marker is a region of homozygosity of 15.77 cM,
between the markers D17S1866 and D17S960; however, the crossover for
the marker D17S1529 refines the region to 10.77 cM within which the
disease gene is predicted to lie. Mutation screening of the nearby RETGC-1 gene, which has been shown to be associated with
LCA1, revealed no mutations in the affected individuals of this family.
Similarly, another prime candidate in the region PEDF was also screened for mutations. The factor has been shown to be
involved in the photoreceptor differentiation and neuronal survival. No
mutations were found in this gene either. Furthermore, RETGC-1 was physically excluded from the critical
disease region based on the existing physical map.
conclusions. It is therefore suggested that this combined phenotype maps to a new
locus and is due to an as yet uncharacterized gene within the 17p13
This PDF is available to Subscribers Only