Discovery of a novel genetic variation in papillorenal syndrome
Keywords:optic nerve coloboma, optic nerve dysplasia, renal coloboma syndrome, papillorenal syndrome, PAX2 gene
Renal coloboma syndrome or papillorenal syndrome is an autosomal dominant genetic disorder characterized by congenital renal and ocular disorders associated with variations in the PAX2 gene. In this case report, a 46-year-old gentleman presented for ocular examination in the setting of systemic hypertension. Past medical history included a kidney transplant due to renal failure. Fundus examination revealed bilateral optic nerve abnormalities with a large central excavation, with numerous vessels radiating from the periphery of the optic disc, consistent with the Morning Glory anomaly. Optical coherence tomography (OCT) disclosed substantial thinning of retinal nerve fiber layer. Genetic studies revealed the heterozygous variant c.398delC in the 3’ exon of PAX2 gene not previously described in the peer-reviewed medical literature (searched using MEDLINE and cross-referenced literature).
Bower M, Salomon R, Allanson J, et al. Update of PAX2 mutation in renal coloboma syndrome and establishment of a locus-specific database. Human Mutation 2012; 33: 457-66.
Köhler S, Carmody L, Vasilevsky N, et al. Expansion of the human phenotype pntology (HPO) knowledge base and resources. Nucleic Acids Research 2019; 47: D1018-27.
Parsa CF, Silva ED, Sundin OH, et al. Redeﬁning papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity. Ophthalmology 2001; 108: 738-49.
Rachwani Anil R, Rocha-de-Lossada C, Ayala CH, Contreras ME. A new mutation in the PAX2 gene in a Papillorenal Syndrome patient. American Journal of Ophthalmology Case Reports 2019; 16: 100563.
Rieger G. On the clinical picture of Handmann’s anomaly of the optic nerve morning glory syndrome? Klinische Monatsblatter fur Augenheilkunde 1977; 170: 697-706.
Sanyanusin P, McNoe LA, Sullivan MJ, et al. Mutation of PAX2 in two siblings with renal-coloboma syndrome. Human Molecular Genetics 1995; 4: 2183-4.
Schimmenti LA. Genetic and developemental basis of renal coloboma (papillorenal) syndrome. Expert Review of Ophthalmology 2009; 4: 135-44.
Schimmenti LA. Renal coloboma syndrome. European Journal of Human Genetics 2011; 19: 1207-12.
Weaver RG, Cashwell LF, Lorentz W, et al. Optic nerve coloboma associated with renal disease. American Journal of Medical Genetics 1988; 29: 597-605.
Zhang L, Zhai SB, Zhao LY, et al. New PAX2 heterozygous mutation in a child with chronic kidney disease: a case report and review of the literature. BMC Nephrology 2018; 19: 245.
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