A new mutation in the PAX2 gene in a Papillorenal Syndrome patient

Rachwani-Anil, Rahul; Rocha‐de‐Lossada, Carlos; Ayala, C. Hernando; Contreras, M. España

doi:10.1016/j.ajoc.2019.100563

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…However, the relationship between PAX2 variants and C1q nephropathy is still unclear. It is recognized that PAX2 variants are one of the important causes of FSGS, as reported by many studies ( Rachwani Anil et al, 2019 ; Vivante et al, 2019 ; Nagano et al, 2020 ). The systemic activation of complement in primary FSGS has been identified ( Huang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 92%

Detection of De Novo PAX2 Variants and Phenotypes in Chinese Population: A Single-Center Study

et al. 2022

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Background:PAX2 is a nuclear transcription factor gene that is highly conserved among species. Variants within PAX2 could result in optic nerve colobomas and kidney hypoplasia. However, little clinical and genetic information is currently available about PAX2 variants in Chinese children.Objective: This study aims to further understand the clinical manifestations and genetic characteristics of PAX2 variants in Chinese population.Methods: In this single-center retrospective study, we analyzed the clinical data of 10 children identified as carriers of PAX2 variants by gene sequencing. All the variants found in this study were analyzed using in silico prediction and American College of Medical Genetics and Genomics (ACMG) standards and guidelines.Results: The mean age for developing the first symptom in 10 unrelated children was 7.2 years old. Proteinuria and bilateral kidney dysplasia were found in every patient. Two children underwent kidney histological examination; one child showed high-intensity C1q deposition in the kidney, and the other child showed focal segmental glomerular sclerosis (FSGS). Three children had PAX2-related ocular abnormalities, including nystagmus, retinal exudation, amblyopia, microphthalmia, microcornea, and total blindness. In addition, one patient had the comorbidity of oculocutaneous albinism (OCA). Eight different PAX2 variants were found in ten patients, three of which were reported for the first time.Conclusion: We reported some patients with unique manifestations and comorbidities, and we reported three variants that have not been previously identified. The PAX2 gene is prone to spontaneous variants, and the outcome of patients is unfavorable. Because of the lack of specific therapy, genetic testing should be recommended for individuals with obvious evidence of kidney dysplasia and eye abnormalities, and kidney protective treatment should be initiated early.

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Section: Discussionmentioning

confidence: 92%

Detection of De Novo PAX2 Variants and Phenotypes in Chinese Population: A Single-Center Study

et al. 2022

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“…A follow-up study in a pediatric cohort of steroid-resistant nephrotic syndrome and FSGS presented additional evidence of phenotypic expansion of extremely rare pathogenic PAX2 SNVs with the identification of heterozygous missense SNVs in 1.3% of cases [12]. Since the publication of these landmark papers, others, too, have reported on the incidence of PAX2 mutations in nonsyndromic FSGS (see Table 1) [35‒42].…”

Section: Pax2: a Kidney Development Gene Attributed To Cause Isolated...mentioning

confidence: 99%

Developmental Causes of Focal Segmental Glomerulosclerosis

Shane Klomp,

Levtchenko,

Westland

2024

Glomerular Dis

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Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS. Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture. The discovery of deleterious single-nucleotide variants in PAX2, a transcription factor crucial in normal kidney development and a known cause of papillorenal syndrome, in individuals with adult-onset FSGS without congenital kidney defects has shed new light on developmental defects that become evident during podocyte injury. Key Message: In this mini-review, we challenge the assumption that FSGS in CAKUT is caused by glomerular hyperfiltration alone and hypothesize a multifactorial pathogenesis that includes overlapping cellular mechanisms that are activated in both damaged podocytes as well as nephron progenitor cells.

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“…Refractive error is common [ 39 ]. Complications include perifoveal splitting, optic nerve atrophy and bilateral glaucomatous cupping [ 34 , 35 ]. There is no treatment.…”

Section: Common Ocular Abnormalities In Genetic Forms Of Fsgsmentioning

confidence: 99%

Ocular manifestations of the genetic causes of focal and segmental glomerulosclerosis

et al. 2023

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Genetic forms of focal and segmental glomerulosclerosis (FSGS) often have extra-renal manifestations. This study examined FSGS-associated genes from the Genomics England Renal proteinuria panel for reported and likely ocular features. Thirty-two of the 55 genes (58%) were associated with ocular abnormalities in human disease, and a further 12 (22%) were expressed in the retina or had an eye phenotype in mouse models. The commonest genes affected in congenital nephrotic syndrome (NPHS1, NPHS2, WT1, LAMB2, PAX2 but not PLCE1) may have ocular manifestations . Many genes affected in childhood–adolescent onset FSGS (NPHS1, NPHS2, WT1, LAMB2, SMARCAL1, NUP107 but not TRPC6 or PLCE1) have ocular features. The commonest genes affected in adult-onset FSGS (COL4A3–COL4A5,GLA ) have ocular abnormalities but not the other frequently affected genes (ACTN4, CD2AP, INF2, TRPC6). Common ocular associations of genetic FSGS include cataract, myopia, strabismus, ptosis and retinal atrophy. Mitochondrial forms of FSGS (MELAS, MIDD, Kearn’s Sayre disease) are associated with retinal atrophy and inherited retinal degeneration. Some genetic kidney diseases (CAKUT, ciliopathies, tubulopathies) that result in secondary forms of FSGS also have ocular features. Ocular manifestations suggest a genetic basis for FSGS, often help identify the affected gene, and prompt genetic testing. In general, ocular abnormalities require early evaluation by an ophthalmologist, and sometimes, monitoring or treatment to improve vision or prevent visual loss from complications. In addition, the patient should be examined for other syndromic features and first degree family members assessed.

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A new mutation in the PAX2 gene in a Papillorenal Syndrome patient

Cited by 5 publications

References 16 publications

Detection of De Novo PAX2 Variants and Phenotypes in Chinese Population: A Single-Center Study

Detection of De Novo PAX2 Variants and Phenotypes in Chinese Population: A Single-Center Study

Developmental Causes of Focal Segmental Glomerulosclerosis

Ocular manifestations of the genetic causes of focal and segmental glomerulosclerosis

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