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K. Linkroum, E. A. DelBono, J. L. Wiggs; Identification of Deletion Breakpoints in a Patient With Rieger Syndrome and a Chromosome 13 Deletion and Screening of Candidate Genes in the Deleted Region. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1727.
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© ARVO (1962-2015); The Authors (2016-present)
To identify the deletion breakpoints in a patient with Rieger syndrome and a chromosome 13 deletion and to screen candidate genes in the deleted interval for mutations in families affected by autosomal dominant anterior segment dysgenesis and early onset glaucoma.
Genomic DNA samples from a patient with Rieger syndrome and a cytogenetically detected deletion of chromosome 13q14-q31 and his parents were used for deletion boundary mapping using microsatellite markers distributed throughout chromosome 13. Genomic DNA samples from twenty-eight families and 18 isolated patients affected with autosomal dominant anterior segment dysgenesis and early onset glaucoma were used to analyze candidate genes located in the deletion region. Candidate genes were evaluated by PCR amplification of individual exons, direct sequencing using BIGDYE chemistries and an automated ABI 3100 sequencer, and analysis with Vector NTI software.
Deletion breakpoint mapping identified a 35Mb deleted region in a male patient with Rieger syndrome extending from marker D13S273 to D13S1235. Within this deleted region, five candidate genes (DACH1, SPRY2, POU4F1, SLAIN1, and KLF12) with ocular expression and possible developmental regulatory function were screened for mutations in the probands of 28 families with autosomal dominant anterior segment dysgenesis and 18 sporadic cases. Two potentially interesting DNA sequence variants have been identified: a nonsynonymous SNP in DACH1 (S555P) was found in one sporadic patient, and a nonsynonymous SNP in POU4F1 (T95A) was found in another sporadic case. Neither of these changes were found in 200 control chromosomes, and both changes are located in conserved regions of the proteins. Family members were not available for further testing.
These results identify a 35Mb region on chromosome 13 that could contain a gene responsible for anterior segment dysgenesis. Candidate gene analysis has identified two potential mutations in developmental regulatory genes with ocular expression that have not been identified in over 200 control chromosomes. Additional families will be analyzed for mutations in these genes and additional candidate genes are also under analysis.
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