Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome

Abstract

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 gene. In this article, the authors present four patients with PAPRS who are carriers of three new mutations, as well as another patient with a possible non-pathogenic variant of the gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for . 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 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 mutations, which until now have not been described in the current literature; another patient with a new mutation showing only ocular manifestations of the disease, and lastly, a patient who is a carrier of a variant of the gene has a congenitally abnormal optic disc, which is probably not related to PAPRS.

Decreased Microglia in Pax2 Mutant Mice Leads to Impaired Learning and Memory

“…A growing number of studies suggested that transcription factors play an important role in the process of neural development, and multiple genes encoding transcription factors had been identified as risk genes for neurodevelopmental disorders. , The transcription factor encoded by the Pax2 gene is expressed in the kidneys, eyes, ears, and CNS − and participates in the differentiation of early neural precursor cells. Mutations in Pax2 result in various diseases, such as renal dysplasia, abnormalities of the optic nerve, , and neurodevelopment disorders, including developmental delays, , epilepsy, , ID, , and ASD . In previous studies, we found that Pax2 +/– mice showed a high level of self-grooming behavior compared with wild-type mice .…”

“…24,25 The transcription factor encoded by the Pax2 gene is expressed in the kidneys, eyes, ears, and CNS 26−28 and participates in the differentiation of early neural precursor cells. Mutations in Pax2 result in various diseases, such as renal dysplasia, abnormalities of the optic nerve, 29,30 and neurodevelopment disorders, including developmental delays, 31,32 epilepsy, 33,34 ID, 35,36 and ASD. 36 In previous studies, we found that Pax2 +/− mice showed a high level of self-grooming behavior compared with wild-type mice.…”

Retinal oxygen saturation and vessel diameter in patients with chronic kidney disease

“…Although this study did not observe retinal haemorrhage or aneurysm formation, the oxygen saturation in larger retinal vessels was a marker of both retinal metabolism and vascular function, and this parameter could contribute to early detection and prevention of the development of microcirculatory dysfunction in CKD. The constellation of optic nerve abnormalities and renal disease has been described in recent years as papillorenal syndrome (PAPRS), an autosomal dominant genetic disorder associated with PAX2 mutations (Parsa et al 2001;Galvez-Ruiz et al 2017). Papillorenal syndrome (PAPRS) was first described in 1977 by Rieger, when it was termed renal coloboma syndrome (Rieger 1977), having later been redefined as PAPRS (Parsa et al 2001).…”

“…The constellation of optic nerve abnormalities and renal disease has been described in recent years as papillorenal syndrome (PAPRS), an autosomal dominant genetic disorder associated with PAX2 mutations (Parsa et al 2001; Galvez‐Ruiz et al 2017). Papillorenal syndrome (PAPRS) was first described in 1977 by Rieger, when it was termed renal coloboma syndrome (Rieger 1977), having later been redefined as PAPRS (Parsa et al 2001).…”

The Role of PAX2 in Neurodevelopment and Disease

“… 37 For example, the deletion of cytosine in exon 5 of patient 13 causes increased gene expression and exhibits seizures ( Table 1 ). The insertion of guanine in exon 2 of patients 3–6, which may cause premature termination of transcription and change the DNA binding function of PD, 21 resulting in insufficient PAX2 haplotypes, affecting protein function, and may cause patients to exhibit developmental delays and intellectual disability. While Pax2 consists of 10 exons spanning approximately 91.7 kb in mice, the corresponding translated peptide sequences of human and mouse exon 6 are identical.…”