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P. Jaru-ampornpan, J. Kuchtey, R. W. Kuchtey; Screening Angiopoietin-Like 7 in Primary Congenital Glaucoma Patients. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2167.
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Angiopoietin-like-7 (ANGPTL7) is a candidate glaucoma gene located on human chromosome 1p36, within the GLC3B locus, which is one of 3 identified loci for primary congenital glaucoma (PCG). ANGPTL7 protein is elevated in glaucomatous aqueous humor and trabecular meshwork and its overexpression can be induced by both dexmethasone and Transforming Growth Factor beta, suggesting it may contribute to glaucoma pathogenesis. The purpose of this study is to develop an assay for identifying potential disease-causing mutations in the ANGPTL7 gene.
DNA was extracted from blood samples taken from ten PCG probands identified at the Vanderbilt Eye Institute glaucoma clinic, as well as their family members, when available. All probands were initially screened for mutations in the Cytochrome P450 1B1 (CYP1B1) gene by DNA sequencing using published primers. Probands without disease-associated genetic variants in CYP1B1 were then screened for genetic variants in ANGPTL7 by DNA sequencing using primers designed with Primer 3 software and comparison with the reference sequence. ANGPTL7 sequence was determined for relatives of probands with genetic variants found in ANGPTL7.
Ten probands (6 male, 4 female) from 9 families ranging in age from 7 months to 55 years were included in this study. These patients included 8 Caucasians, 1 African American and one Hispanic. Initial screening of the probands revealed no previously reported or novel mutations in the CYP1B1 coding region. Therefore, all 10 probands were eligible for screening for mutations in ANGPTL7. One patient was found to be heterozygous for Gln175His (CAG -> CAT) in ANGPTL7 exon 3. This rare mutation has been previously reported in the SNP database with a heterozygosity of 0.010, but a functional implication for this missense mutation has not been determined. Parents and an older sibling of this patient were screened for this specific mutation. Identical heterozygous status was also found in the patient’s mother, who is free of glaucoma, suggesting that this SNP does not co-segregate with the disease. Another proband showed a homozygous C -> G mutation at position 1355 and heterozygous A -> G mutation at position 1380 (GenBank Accession Number AF350361.1). These two SNPs are located greater than 1500 bp upstream to the starting codon, and have not yet been identified to influence transcription of ANGPTL7.
A PCR-based assay was developed to screen ANGTPL7 as a candidate for human PCG. Three SNPs were identified in this small data set using this assay. Although these SNPs are not likely disease-causing, this assay can be used for future studies.
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