Renal coloboma syndrome is an autosomal dominant genetic disorder that primarily affects kidney and eye development. It is also known as papillorenal syndrome. People with this condition typically have kidneys that are small and underdeveloped (hypodysplastic), which can lead to end-stage renal disease. It has been estimated that approximately 10% of children with hypoplastic kidneys may have renal coloboma syndrome. The eye anomalies consist of a wide and dysplastic optic disk with the emergence of the retinal vessels from the periphery of the disk, frequently called optic nerve coloboma.

We report the ocular findings of a Caucasian female with papillorenal syndrome (PAPRS) from a de novo PAX2 mutation. She presented to our clinic with early-onset end-stage renal disease. Ophthalmologic exam revealed bilateral band keratopathy, abnormal optic disc configuration, and Elschnig spots, with preserved visual acuity. Genomic sequencing revealed a heterozygous nonsense PAX2 mutation (C > G p. (Tyr73*) at position 219 in exon 3) associated with PAPRS. Parents of the proband did not display phenotypic features of PAPRS and were confirmed to be without the PAX2 mutation.

UNASSIGNED: Papillorenal syndrome is an autosomal dominant disorder associated with mutations in the gene PAX2 and often presents with characteristic and specific optic disc findings, frequently with renal dysplasia. In at least half of cases, an identifiable mutation in the PAX2 gene can be detected. We report the ocular findings in a second case of papillorenal syndrome with the c.350 G > C (p.Arg117Pro) mutation detected within the PAX2 gene.
UNASSIGNED: A case report of papillorenal syndrome due to PAX2 mutation. Complete ophthalmologic examination was performed as well as color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Genetic testing was performed using a next-generation sequencing with CNV calling (NGS-CNV) panel test containing 55 genes associated with nephrotic syndrome or focal segmental glomerulosclerosis.
UNASSIGNED: An 11-year-old boy who presented with hypertension and proteinuria was found to have stage IV chronic kidney disease. Presenting visual acuity was 20/25 in the right eye and 20/20 in the left eye. The fundus exam showed bilateral centrally excavated optic discs with absent central retinal vessels and a compensatory multiplicity of cilioretinal vessels, characteristic and specific for papillorenal syndrome. OCT showed outer retinal atrophy and macular schisis. Genetic testing identified the likely pathogenic c.350 G > C (p.Arg117Pro) mutation in PAX2.
UNASSIGNED: We report the first description, to our knowledge, of the clinical presentation, ocular and systemic findings, and ophthalmic imaging in an individual with papillorenal syndrome associated with the PAX2 c.350 G > C (p.Arg117Pro) mutation. Our case adds to the current understanding of papillorenal syndrome and demonstrates that this condition is associated with a pathognomonic optic disc appearance and significant renal disease.

UNASSIGNED: Papillorenal syndrome (PAPRS) is a rare inherited disorder often involves abnormalities of eye and kidney. Paired box 2 (PAX2) gene, which is widely expressed in the development of the organs including kidney, ureter, eye, ear, and central nervous system has been considered an underlying cause of PAPRS. The present work aims to further our understanding of PAX2 gene and PAPRS by reporting a family with PAPRS associated with a novel PAX2 mutation and describing ocular manifestation of PAX2 mutation in previous literatures.
UNASSIGNED: We herein present a family with PAPRS presented with typical congenital optic disc defects and mild renal dysplasia. Through screening of candidate genes based on the next-generation sequencing, the heterozygous PAX2 mutation c.175C > T (p. Arg59Trp) was identified which had never been reported.
UNASSIGNED: The study expands the genetic and clinic spectrum of PAPRS. Further review of detailed ocular manifestation and genotypes of PAX2 mutation in previous study improves the recognition of the ocular phenotypes\' spectrum, assists in the identification of PAPRS. Moreover, this study reveals that PAPRS is a systemic disorder with heterogeneous diverse phenotypes, and shows the importance of gene panel sequencing in the diagnosis of PAPRS which could achieve high diagnostic rates.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage renal disease in children. Diagnosis by genetic testing has proven challenging due to its genetic and phenotypic heterogeneity, as well as incomplete penetrance. We report a case on a 16-months old female with a history of renal cysts and a PAX2 mutation.
METHODS: The patient presented with a prenatal diagnosis of Potter sequence and a postnatal diagnosis of renal cysts. An ultrasound at 20 weeks gestation revealed right renal agenesis and possible left renal dysplasia. Post natal genetic analyses identified a novel mutation in PAX2.
CONCLUSIONS: Cystic kidney disease is often underdiagnosed due to its variable expressivity and wide range of clinical manifestations; PAX2 genetic screening should be considered for all patients with CAKUT.

Hereditary hyperuricemia may occur as part of a syndromic disorder or as an isolated nonsyndromic disease, and over 20 causative genes have been identified. Here, we report the use of whole genome sequencing (WGS) to establish a diagnosis in a family in which individuals were affected with gout, hyperuricemia associated with reduced fractional excretion of uric acid, chronic kidney disease (CKD), and secondary hyperparathyroidism, that are consistent with familial juvenile hyperuricemic nephropathy (FJHN). However, single gene testing had not detected mutations in the uromodulin (UMOD) or renin (REN) genes, which cause approximately 30-90% of FJHN. WGS was therefore undertaken, and this identified a heterozygous c.226G>C (p.Gly76Arg) missense variant in the paired box gene 2 (PAX2) gene, which co-segregated with renal tubulopathy in the family. PAX2 mutations are associated with renal coloboma syndrome (RCS), which is characterized by abnormalities in renal structure and function, and anomalies of the optic nerve. Ophthalmological examination in two adult brothers affected with hyperuricemia, gout, and CKD revealed the presence of optic disc pits, consistent with optic nerve coloboma, thereby revising the diagnosis from FJHN to RCS. Thus, our results demonstrate the utility of WGS analysis in establishing the correct diagnosis in disorders with multiple etiologies.

UNASSIGNED: To present a new mutation in a patient with Papillorenal Syndrome (PAPRS).
UNASSIGNED: PAPRS is an autosomal dominant disease that involves ocular and renal abnormalities. We present a patient with PAPRS with a genetically diagnosed PAX2 and new pathogenic mutation. A complete ophthalmological, neurological, nephrological and Ears-Nose-Throat (ENT) examination were undertaken. The patient suffered from Focal Segmental Glomerulosclerosis (FSGS) and some typical ophthalmological signs of PAPRS, including optic nerve coloboma and optic disc pit (ODP) maculopathy associated with an abnormal retinal vessel distribution and numerous cilioretinal arteries in the right eye. The left eye showed similar vessel abnormalities although the optic disc had a normal morphology.
UNASSIGNED: A new mutation in the PAX2 gene was identified in a patient with ocular and renal abnormalities.

Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an autosomal dominant disease characterised by the presence of congenital renal and optic nerve abnormalities associated with mutations of the PAX2 gene. In this article, the authors present four patients with PAPRS who are carriers of three new PAX2 mutations, as well as another patient with a possible non-pathogenic variant of the PAX2 gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2 presented with the classic signs of PAPRS: renal disease associated with a congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a congenital optic nerve abnormality and no renal involvement. In patients 1 and 2, the optic nerves were affected by the presence of a central excavation within the optic disc, absence of the central retinal artery, as well as multiple cilioretinal arteries radiating from the periphery of the optic disc. Bilateral optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the presence of superficial gliotic tissue on the left optic disc. All patients presented with a missense mutation in the PAX2 gene, where in patient 4 possibly being only a non-pathogenic variant of the gene. In conclusion, the authors present two patients with classic clinical signs of PAPRS, having two new PAX2 mutations, which until now have not been described in the current literature; another patient with a new PAX2 mutation showing only ocular manifestations of the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene has a congenitally abnormal optic disc, which is probably not related to PAPRS.

Papillorenal syndrome (PRS), an autosomal dominant inherited condition, is clinically featured by renal hypoplasia and optic nerve dysplasia. Based on current knowledge of genotype-phenotype correlations in PRS, mutations in the Paired box 2 (PAX2) gene have been recognized as a critical pathogenesis of typical renal and optic disease manifestations. However, little information is currently available on the skeletal abnormalities of PRS and the potential contribution of PAX2 mutations. Here, we present a case of a 10-year-old female PRS patient with the typical features of chronic renal failure and severe myopia, but was unexpectedly discovered camptodactyly of her left middle finger which affects the proximal interphalangeal joint. Pathologically, the camptodactyly was further indicated by radiology as a skeletal deformity, demonstrating a decline of bone mineral density and disappearance of joint space. Molecular diagnostics revealed a heterozygous mutation, 220_225dup, in the exon 3 of her PAX2 gene, which is de novo considering the lack of this mutation in her non-consanguineous parents. This mutation leads to duplication of glutamic acid at position 74 and tyrosine at position 75 in PAX2 protein, which may influence the DNA-binding function. Besides, the absence of Spalt like transcription factor 4 (SALL4) mutation excluded the diagnosis of acro-renal-ocular syndrome (AROS), of which clinical characteristics are similar to our patient\'s. This case unravels a previously unrecognized phenotype of camptodactyly due to a significant skeletal deformity of PRS with a heterogeneous PAX2 mutation of hexanucleotide duplication. This report challenges against the current belief of genotype-phenotype correlations in PRS.