thin basement membrane disease

INTRODUCTION: IgA nephropathy is the most common primary glomerulonephritis among adults in clinic. Thin basement membrane nephropathy is often underestimated or even omitted if it coincides with IgA nephropathy. Therefore, it is necessary to study the epidemiological, clinical, and molecular characteristics of the concurrence of this entity. METHODS: Eight patients with concurrent IgA nephropathy and thin basement membrane nephropathy (IgA-T) were retrospectively analyzed based on their clinicopathological characteristics...

OBJECTIVE: Amelogenesis imperfecta (AI) is defined as inherited enamel malformations. LAMA3 (laminin alpha-3) encodes a critical protein component of the basement membrane (laminin-332). Individuals carrying heterozygous LAMA3 mutations have previously been shown to have localized enamel defects. This study aimed to define clinical phenotypes and to discern the genetic etiology for four AI kindreds. MATERIALS AND METHODS: Whole exome analyses were conducted to search for sequence variants associated with the disorder, and micro-computed tomography (μCT) to characterize the enamel defects...

Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4 , which also cause late-onset focal segmental glomerulosclerosis (FSGS) or autosomal dominant Alport syndrome (ADAS). Thirteen TBMN cases were analyzed using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and exome sequencing. Ten heterozygous variants were detected in COL4A3 or COL4A4 in nine patients via Sanger sequencing, three of which were novel variants...

No abstract text is available yet for this article.

PURPOSE: This study aimed to examine tubulointerstitial B-cell infiltration in patients with adult-onset immunoglobulin A vasculitis (IgAV) and nephritis (IgAV-N), and to evaluate whether B-cell infiltration correlated with clinicopathological variables at kidney biopsy and with short-term renal outcomes. METHODS: Twenty patients with adult-onset IgAV-N and 10 control patients with thin basement membrane nephropathy (TBMN) were retrospectively examined. The lymphatic organization was graded based on B-cell infiltration and was classified into 4 groups: 0-T cells without B cells, 1-scattered B and T cells, 2-clustered B and T cells, and 3-nodular compartmentally arranged B- and T-cell aggregates, equivalent to tertiary lymphoid tissue (TLT)...

BACKGROUND: Thinned glomerular basement membrane (tGBM) lesions are not uncommon in IgA nephropathy (IgAN). Type IV collagen-built of α 3, α 4, and α 5 chains, encoded by COL4A3 / COL4A4 / COL4A5 genes-is the major component of glomerular basement membrane (GBM). In recent years, mutations in type IV collagen-encoding genes were also reported in patients with a histologic diagnosis of FSGS. Pathogenic COL4A3 / COL4A4 / COL4A5 variants were recently identified in familial cases of IgAN, but the contribution of these variants to sporadic IgAN is still unclear...

Background: Despite increasing recognition that CKD may have underlyi ng genetic causes, genetic testing remains limited. This study evaluated the diagnostic yield and phenotypic spectrum of CKD in individuals tested through the KIDNEYCODE sponsored genetic testing program. Methods: Unrelated individuals who received panel testing (17 genes) through the KIDNEYCODE sponsored genetic testing program were included. Individuals had to meet at least one of the following eligibility criteria: eGFR ≤90 ml/min per 1...

Disease-causing variants in COL4A3- 5 are associated with type-IV-collagen-related nephropathy, a genetically and phenotypically multifaceted disorder comprising Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) and autosomal, X-linked and a proposed digenic inheritance. Initial symptoms of individuals with AS are microscopic hematuria followed by proteinuria leading to kidney failure (90% on dialysis < age 40 years). In contrast, individuals with TBMN, an outdated histology-derived term, present with microscopic hematuria, only some of them develop kidney failure (>50 years of age)...

The term "autosomal dominant (AD) Alport syndrome" is often used to describe the condition associated with heterozygous pathogenic COL4A3 or COL4A4 variants and has largely replaced "thin basement membrane nephropathy (TBMN)." AD Alport syndrome implies that affected individuals develop end-stage kidney failure (ESKF) as well as the typical Alport hearing loss and ocular abnormalities, but these features have been considered rare with TBMN. Recent studies suggest that ESKF occurs in 14% to 30% of those with heterozygous pathogenic COL4A3 or COL4A4 variants but confirm that the hearing loss and ocular defects occur uncommonly if at all...

No abstract text is available yet for this article.

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently described, rare renal tumor that differs clinically, morphologically, and molecularly from papillary renal cell carcinoma (RCC). To further characterize the pathological spectrum of this rare tumor, in this study, we retrospectively identified 16 cases of PRNRP from three institutions to comprehensively investigate the clinicopathological and molecular genetic features, using immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and targeted next-generation sequencing (NGS)...

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia...

BACKGROUND: The inflammatory bowel disease, containing Crohn's disease and ulcerative colitis, was rare in the population, especially in the complication of kidney disease. A few studies had found proteinuria played a potential indicator of inflammatory bowel disease occurrence and activity. This study aimed to better define the histopathologic spectrum and study the outcome of renal disease in Crohn's disease. METHODS: A retrospective study of 3557 Crohn's disease from January 1st , 2016 to July 1st , 2021 in the Sixth Affiliated Hospital of Sun Yat-sen University identified 20 (0...

A ureterocele is a rare congenital anomaly with cystic dilation of the terminal segment of the ureter entirely within the bladder (orthotopic) or associated with ectopic ureter (ectopic). Its aetiology has not been fully clarified; however, it may involve genetic or acquired factors. Urothelial carcinoma (UC) is the most common type of canine urinary tract neoplasm, among which over 90% of cases are invasive. The non-papillary (flat) non-infiltrating form accounts for a very small percentage of canine UCs and is considered carcinoma in situ (CIS)...

Human skin comprises stratified squamous epithelium and dermis with various stromal cells and the extracellular matrix (ECM). The basement membrane (BM), a thin layer at the top of the dermis, serves as a unique niche for determining the fate of epidermal stem cells (EpSCs) by transmitting physical and biochemical signals to establish epidermal cell polarity and maintain the hierarchical structure and function of skin tissue. However, how stem cell niches maintain tissue homeostasis and control wound healing by regulating the behavior of EpSCs is still not completely understood...

No abstract text is available yet for this article.

Pathologists use multiple microscopy modalities to assess renal biopsy specimens. Besides usual diagnostic features, some changes are too subtle to be properly defined. Computational approaches have the potential to systematically quantitate subvisual clues, provide pathogenetic insight, and link to clinical outcomes. To this end, a proof-of-principle study is presented demonstrating that explainable biomarkers through machine learning can distinguish between glomerular disorders at the light-microscopy level...

School urinary screening programming can be useful for the early detection of renal and urinary disorders. However, urine screening is not included in the school health check-up in our region. Therefore, from February 2012 to March 2021, 12,497 school students were screened for urinalysis, and a long-term follow-up took place via an electronic medical record system. Among these screened students, 719 (5.75%) positive individuals received a repeat urinalysis 2 weeks later. During the 9-year medical record system follow-up period, 5 children had renal biopsies and 2 children had a diagnosis of IgA nephropathy (IgAN), while the remaining 3 children were diagnosed with thin basement membrane disease (TBM), primary nephrotic syndrome (PNS), and were suspected of C3 glomerulopathy, respectively...

The glomerular filtration barrier (GFB) produces primary urine and is composed of a fenestrated endothelium, a glomerular basement membrane (GBM), podocytes, and a slit diaphragm. Impairment of the GFB leads to albuminuria and microhematuria. The GBM is generated via secreted proteins from both endothelial cells and podocytes and is supposed to majorly contribute to filtration selectivity. While genetic mutations or variations of GBM components have been recently proposed to be a common cause of glomerular diseases, pathways modifying and stabilizing the GBM remain incompletely understood...

Alport syndrome (AS) is a genetic kidney disease of basement membrane collagen disorder accounting for approximately 2% of ESRD patients. Next-generation and whole-exome sequencing methods are increasingly frequently used as an efficient tool not only for the diagnosis of AS but also for the establishment of genotype-phenotype correlation. We herein report the identification of a novel heterozygous missense mutation in COL4A3 gene (c.G3566A: p.G1189E) causing variable phenotypes in an ADAS Family based on the combination of clinical, histologic, pedigree, and genetic sequencing information...