Purpose: Cataracts are the most commoncause of blindness worldwide. Inherited cataract is a clinically andgenetically heterogeneous disease. Here we report a novel mutation inthe paired-like homeodomain 3 (PITX3) gene segregating in a fourgeneration English family with an isolated autosomal dominant posteriorpolar cataract. Methods: A genome-wide linkage wasperformed by means of single nucleotide polymorphism (SNP) andmicrosatellite markers. Linkage analyses were performed with theGeneHunter and MLINK programs. Direct sequencing of PCR products wasperformed to detect mutation in the gene, using the BigDye version 3.1and analyzed using Sequence analysis version 5.2. Results: Genome-wide linkage analysiswith SNP markers, identified a disease-haplotype interval on chromosome10q. Two point positive logarithm of odds (LOD) scores was obtainedwith markers D10S205 (Z=3.10 at θ=0.00), flanked by markers D10S1709and D10S543, which harbors the homeobox gene PITX3. Sequenceanalysis of PITX3 revealed a 1-bp deletion that cosegregatedwith all the affected members of this family which resulted in aframeshift in codon 181 and likely to produce an aberrant proteinconsisting of 127 additional residues. Conclusions: The 542delC is a novelmutation in PITX3 causing an isolated posterior polar cataract.
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