scholarly journals Clinical Features and Familial Mutations in an Autosomal-Inherited Alport Syndrome Patient With the Presentation of Nephrotic Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Dahai Wang ◽  
Chunrong Shan ◽  
Xinxin Jing ◽  
Qiuye Zhang ◽  
Hong Chang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Basement Membrane ◽  
Clinical Features ◽  
Alport Syndrome ◽  
Disease Onset ◽  
Poor Response ◽  
Pathogenic Mutation ◽  
Pulse Therapy ◽  
Steroid Resistance ◽  
Type Iv

Background: The aim of this study was to report the clinical features and mutations in a patient with autosomal-inherited Alport syndrome (AS).Methods: We examined the clinical data, mutation analysis results, and family tree of a patient with autosomal-inherited AS, who had nephrotic syndrome as her first manifestation.Results: The proband was a girl of 11 months who presented with nephritic and nephrotic syndromes including gross hematuria but had a normal renal function. Her treatment course was complicated by steroid resistance and a poor response to cyclosporine A and cyclophosphamide pulse therapy. Renal biopsy was performed 2 years after disease onset; light microscopy showed glomerular segmental mesangio-proliferative lesions, and type IV collagen staining showed the loss of the α3 chain in the glomerular and tubular basement membrane (GBM and TBM) and α5 chain loss in the GBM. Electron microscopy showed uneven GBM thickness, with the dense basement membrane (BM) layer obviously delaminated and torn, showing a typical “lace-like” change. The segmental BM was loosened and widened. Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed. We detected a new COL4A4 mutation in the proband, namely c.1715delG (p.G572Vfs * 81) in exon 24. Her father and grandmother carried the same mutation, but her mother and sister did not.Conclusions: We found a new potentially pathogenic mutation of COL4A4 in a patient with autosomal-inherited AS, which presented as nephrotic syndrome in infancy.

Alport Syndrome with a Peculiar Pattern of Distribution of the α3–α6 Chains of Type IV Collagen in Renal Basement Membrane

Nephron ◽  
1998 ◽  
Vol 80 (1) ◽  
pp. 115-117 ◽  
Author(s):  
Mikiya Fujieda ◽  
Fumiko Endo ◽  
Yutaka Morisawa ◽  
Ichiro Naito ◽  
Yoshikazu Sado ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Type Iv

scholarly journals Clinical Features of Idiopathic Nephrotic Syndrome and Factors Associated with its Relapse in Children: A Population-Based Study

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Abolhassan Seyezadeh ◽  
Mohamad Reza Tohidi ◽  
Somaye Sheikhi ◽  
Mohammad Saleh Seyedzadeh ◽  
Sara Hookari
Keyword(s):  
Nephrotic Syndrome ◽  
Recurrence Rate ◽  
Clinical Features ◽  
Idiopathic Nephrotic Syndrome ◽  
Population Based ◽  
Steroid Resistance ◽  
Filtration Barrier ◽  
The Mean ◽  
First Recurrence

Background: Idiopathic Nephrotic Syndrome (INS), which is caused by a defect in the glomerular filtration barrier, is the most common chronic glomerular disease in children. Objectives: The present study aimed to assess the clinical features of INS and some recurrence-related factors in children. Methods: This population-based, cross-sectional study was conducted on 302 children with INS referring to the Pediatric Nephrology Clinic of Imam Reza Hospital of Kermanshah city, Iran, during 1998-2018. Results: The mean age (SD) at the time of diagnosis and the follow-up duration were 4.87 (2.89) years and 49.83 (37.52) months, respectively. The numbers of boys and girls were 185 (61.9%) and 114 (38.1%), respectively. The mean number (SD) of recurrences, annual recurrence rate during the follow-up, and the time to the first recurrence after responding to treatment were 1.71 (1.91), 0.48 (0.77), and 10.15 (10.63) months, respectively. The most common type of INS was steroid-dependent/frequent relapse, with a frequency of 151 (50.5%). Furthermore, 33 (11.0%) and 266 (89.0%) patients were resistant and respondent to treatment, respectively. There was a statistically significant relationship between age at the time of diagnosis and the type of INS (P = 0.007). Conclusions: This study revealed a statistically significant association between higher age and steroid resistance. However, in steroid responders, there was no relationship between gender, age at the time of diagnosis, and the time to the first recurrence, and the recurrence rate.

scholarly journals Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis.

1995 ◽  
Vol 5 (9) ◽  
pp. 1714-1717
Author(s):  
J Ding ◽  
J Stitzel ◽  
P Berry ◽  
E Hawkins ◽  
C E Kashtan
Keyword(s):  
Basement Membrane ◽  
Renal Disease ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
Premature Stop Codon ◽  
Sensorineural Deafness ◽  
Type Iv ◽  
Base Pair Deletion ◽  
Carboxy Terminal

Autosomal recessive Alport syndrome can arise from a mutation in either of the genes COL4A3 and COL4A4 on chromosome 2, which encode, respectively, the alpha 3 and alpha 4 chains of Type IV collagen. This report describes a mutation in COL4A3 in a girl who presented at age 5 with hematuria and proteinuria, lacking any family history of renal disease. Renal biopsy at age 8 showed immunoglobulin A nephropathy and Alport syndrome. Sensorineural deafness developed during adolescence, and the patient's renal disease progressed to terminal renal failure by age 20. She received a living related donor renal allograft at age 20 and developed antiglomerular basement membrane nephritis of the allograft 8 months after transplantation. Amplification and sequencing of exon 5 of COL4A3 (counting from the 3' end of the gene) revealed a 7-base-pair deletion, producing a shift of the reading frame and the creation of a premature stop codon. Each parent was heterozygous for the normal and mutant exon 5 sequences. This mutation in COL4A3 would result in the loss of 222 amino acids from the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The mutant chain would be unable to form trimers with other Type IV collagen alpha chains. In addition, the mutant chain would lack the Goodpasture epitope, which resides in the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The absence of this epitope may underly the subsequent development of anti-glomerular basement membrane nephritis in the allograft.

Alport Syndrome and Thin Glomerular Basement Membrane Nephropathy: A Practical Approach to Diagnosis

2009 ◽  
Vol 133 (2) ◽  
pp. 224-232 ◽  
Author(s):  
Mark Haas
Keyword(s):  
Electron Microscopy ◽  
Basement Membrane ◽  
Renal Biopsy ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
The Past ◽  
Type Iv ◽  
Pathologic Features

Abstract Context.—Alport syndrome and thin glomerular basement membrane nephropathy (TBMN) are genetically heterogenous conditions characterized by structural abnormalities in the glomerular basement membrane and an initial presentation that usually involves hematuria. Approximately 40% of patients with TBMN are heterozygous carriers for autosomal recessive Alport syndrome, with mutations at the genetic locus encoding type IV collagen α3 [α3(IV)] and α4 chains. However, although the clinical course of TBMN is usually benign, Alport syndrome, particularly the X-linked form with mutations in the locus encoding the α5 chain of type IV collagen [α5(IV)], typically results in end-stage renal disease. Electron microscopy is essential to diagnosis of TBMN and Alport syndrome on renal biopsy, although electron microscopy alone is of limited value in distinguishing between TBMN, the heterozygous carrier state of X-linked Alport syndrome, autosomal recessive Alport syndrome, and even early stages of X-linked Alport syndrome. Objectives.—To review diagnostic pathologic features of each of the above conditions, emphasizing the need for immunohistology for α3(IV) and α5(IV) in addition to electron microscopy to resolve this differential diagnosis on a renal biopsy. The diagnostic value of immunofluorescence studies for α5(IV) on a skin biopsy in family members of patients with Alport syndrome also is reviewed. Data Sources.—Original and comprehensive review articles on the diagnosis of Alport syndrome and TBMN from the past 35 years, primarily the past 2 decades, and experience in our own renal pathology laboratory. Conclusions.—Although Alport syndrome variants and TBMN do not show characteristic light microscopic findings and can be difficult to differentiate from each other even by electron microscopy, using a combination of electron microscopy and immunohistology for α3(IV) and α5(IV) enables pathologists to definitively diagnose these disorders on renal biopsy in most cases.

scholarly journals Spectrum of clinical features and type IV collagen  -chain distribution in Chinese patients with Alport syndrome

2006 ◽  
Vol 21 (11) ◽  
pp. 3146-3154 ◽  
Author(s):  
G. Wei ◽  
L. Zhihong ◽  
C. Huiping ◽  
Z. Caihong ◽  
C. Zhaohong ◽  
...  
Keyword(s):  
Clinical Features ◽  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Chinese Patients ◽  
Type Iv ◽  
Collagen Chain

scholarly journals Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport Syndrome

2017 ◽  
Vol 29 (3) ◽  
pp. 949-960 ◽  
Author(s):  
Steven D. Funk ◽  
Raymond H. Bayer ◽  
Andrew F. Malone ◽  
Karen K. McKee ◽  
Peter D. Yurchenco ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Basement Membrane ◽  
Alport Syndrome ◽  
Late Onset ◽  
Congenital Nephrotic Syndrome ◽  
Model Organisms ◽  
Missense Mutations ◽  
Amino Terminal ◽  
Wide Range ◽  
Pierson Syndrome

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient’s nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3−/− mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5+/− females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α3α4α5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.

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