Alport syndrome

Karki, Pratap; Shrestha, JK

doi:10.3126/nepjoph.v1i2.3690

Cited by 4 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AS is a progressive inherited glomerulonephritis [ 1 , 2 ]. Hematuria is the initial presentation at early stage [ 13 ]. Proteinuria emerges with disease progression [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome

Wang

Yue

et al. 2015

PLoS ONE

View full text Add to dashboard Cite

The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria <50 mg/kg/d, 15 cases) and heavy proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.

show abstract

“…AS is a progressive inherited glomerulonephritis [ 1 , 2 ]. Hematuria is the initial presentation at early stage [ 13 ]. Proteinuria emerges with disease progression [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome

Wang

Yue

et al. 2015

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…While the above research focused on lenticonus, retinopathies, and other common ocular abnormalities in AS, Gehrs et al [ 33 ] and Karki and Shrestha [ 41 ] reported on 2 separate patients who had macular flecks (also known as retinal flecks), tiny lesions on the macula of the retina. Jeffrey et al [ 40 ] also discovered flecks in 20 patients after conducting an electrophysical study.…”

Section: Resultsmentioning

confidence: 99%

“…One study referenced cataract surgery as a potential solution to vision loss following lenticonus but noted how the procedure can be difficult in certain patients due to elasticity of the thin capsular bag during the capsulorrhexis [ 29 ]. Although cataract surgeries are common, patients with AS seem to develop cataracts at higher rates due an increase of small ruptures in the lens capsule [ 28 , 29 , 41 , 42 , 44 , 45 ]. A cataract is diagnosed by a visual acuity test or slit-lamp examination.…”

Section: Resultsmentioning

confidence: 99%

“…is entire process is summarized as a flow diagram in Figure 1. Of the 23 included studies, twelve were case studies on an individual or a group of patients [30,33,35,37,39,41,[43][44][45][46][47]50], two were prospective studies [29,38], three were retrospective studies [31,32,49], and six were mixed methodology studies that did not meet the previous three categories [28,34,36,40,42,48] (Table 1). 20 studies reported AS ocular abnormalities only [28,[30][31][32][33][34][35][36][37][38][40][41][42][43][44][45][46][47][48][49], and the remaining 3 studies reported both ocular abnormalities and potential medical treatments [29,39,…”

Section: Study Selection and Study Characteristicsmentioning

confidence: 99%

See 1 more Smart Citation

Ocular Manifestations and Potential Treatments of Alport Syndrome: A Systematic Review

Ramakrishnan

Shenoy

Meyer

2022

Journal of Ophthalmology

View full text Add to dashboard Cite

Objectives. Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive research on AS in relation to auditory and renal disorders, more research is needed on the ocular presentations of AS. This systematic review aims to summarize the common ocular abnormalities in patients with AS and to explore the potential treatment options for these irregularities. Methods. The PubMed, MEDLINE, and EMBASE databases were systematically searched from January 1977 to April 2022. Only papers that were published in the English language and explored the ocular abnormalities in AS patients were selected. We manually searched reference lists of included papers for additional studies. Results. A total of 23 articles involving 195 patients were included in this review. The common ocular manifestations in AS patients are lenticonus, macular holes, fleck retinopathy, and thinning of the macula. Although published literature has described the use of cataract surgeries and vitrectomies as standard surgical techniques to alleviate ocular abnormalities in non-AS patients, it must be noted that surgical techniques have not been evaluated in a large research study as a solution for AS abnormalities. Another prospective treatment for AS is gene therapy through the reversion of causative COL4 variants to wild type or exon-skipping therapy for X-linked AS with COL4A5 truncating mutations. Gene therapy, however, remains unable to treat alterations that occur in the fetal and early development phase of the disease. Conclusions. The review found no definitive conclusions regarding the efficacy and safety of surgical techniques and gene therapy in AS patients. Recognition of ocular abnormalities through an ophthalmic examination with an optical coherence tomography (OCT) and slit-lamp examination is critical to the medical field, as ophthalmologists can aid nephrologists and other physicians in diagnosing AS. Early diagnosis and care can minimize the risk of detrimental ocular outcomes, such as blindness and retinal detachment.

show abstract

“…Alport syndrome is often accompanied by hematuria, sensorineural deafness, and ocular abnormalities [ 20 ]. No abnormality in the eye, blood system, and heart ultrasound was observed in this case.…”

Section: Discussionmentioning

confidence: 99%

Compound Mutations of the COL4A3 including a Novel Allele Identified in a Patient with Alport Syndrome

Wang

Jiang

Jin

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Alport syndrome (AS) is a hereditary nephropathy which is characterized by molecular abnormalities in collagen IV. Here, we report compound mutations of the COL4A3 gene including a novel allele identified in a patient with Alport syndrome. The patient was a 25-year-old Chinese woman. She has a history of proteinuria and hematuria with cleft lip and palate. The pathologic results were consistent with Alport syndrome. The patient received ACEI treatment but did not respond well to the treatment. Sequencing results revealed that the patient carried two heterozygous mutations in the COL4A3 gene, including a known mutation (c.4243G>C, p.G1415R), which was inherited from her father, and a previously undescribed allele (c.4216G>A, p.G1406R) inherited from her mother. To date, at least 294 different variants of COL4A3 have been reported according to the Human Gene Mutation Database (HGMD). Identification of c.4216G>A as a new AS-related mutation may contribute to both genetic diagnosis of AS and further functional study of COL4A3.

show abstract

Alport syndrome

Cited by 4 publications

References 0 publications

The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome

The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome

Ocular Manifestations and Potential Treatments of Alport Syndrome: A Systematic Review

Compound Mutations of the COL4A3 including a Novel Allele Identified in a Patient with Alport Syndrome

Contact Info

Product

Resources

About