scholarly journals Mutation in alpha 5(IV) collagen chain gene in nonfamilial hematuria.

1995 ◽  
Vol 6 (2) ◽  
pp. 264-268
Author(s):  
K Kitagawa ◽  
K Nakanishi ◽  
K Iijima ◽  
H Nishio ◽  
Y Sado ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Chain Reaction ◽  
Col4a5 Gene ◽  
Abnormal Expression ◽  
Type Iv ◽  
Polymerase Chain

Alport syndrome is an inherited disorder characterized by progressive nephritis with ultrastructural basket-weave changes of the glomerular basement membrane and neurosensory deafness. Mutations in the COL4A5 gene encoding the Type IV collagen alpha 5 chain have been reported to occur in patients with X-linked Alport syndrome. A girl with hematuric nephritis, characteristic basket-weave glomerular basement membrane changes, and abnormal expression of the Type IV collagen alpha 5 chain immunohistochemically, but no family history of nephritis, was identified. Mutation detection enhancement gel electrophoresis of the polymerase chain reaction-amplified exons of COL4A5 from this patient revealed a sequence variant in the exon 50 region. Sequence analysis of her polymerase chain reaction product demonstrated a single-base (C; nucleotide 4728 from the 5' end) deletion in exon 50. This novel mutation alters the reading frame and introduces a translation stop codon that would be expected to result in a noncollagenous domain with only 209, instead of the normal 229, amino acid residues. Gene tracking with restriction enzyme AfIIII demonstrated that her mother was normal. These findings represent a new mutation of the X-linked Alport syndrome in this patient and demonstrate that a COL4A5 gene mutation causes the abnormal expression of Type IV collagen alpha 5 chain protein.

scholarly journals The contribution of increased collagen synthesis to human glomerulosclerosis: a quantitative analysis of alpha 2IV collagen mRNA expression by competitive polymerase chain reaction.

1992 ◽  
Vol 176 (6) ◽  
pp. 1571-1576 ◽  
Author(s):  
E P Peten ◽  
L J Striker ◽  
M A Carome ◽  
S J Elliott ◽  
C W Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polymerase Chain Reaction ◽  
Reverse Transcription ◽  
Collagen Synthesis ◽  
Type Iv Collagen ◽  
Chain Reaction ◽  
Collagen Mrna ◽  
Type Iv ◽  
Polymerase Chain

We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). alpha 2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process.

scholarly journals Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: a study of 250 patients with hematuria and suspected of having Alport syndrome.

1996 ◽  
Vol 7 (5) ◽  
pp. 702-709 ◽  
Author(s):  
N Heiskari ◽  
X Zhang ◽  
J Zhou ◽  
A Leinonen ◽  
D Barker ◽  
...  
Keyword(s):  
Hot Spots ◽  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Polymerase Chain Reaction Amplification ◽  
Col4a5 Gene ◽  
Type Iv ◽  
Reaction Amplification ◽  
Male Patients ◽  
Polymerase Chain ◽  
Collagen Genes

Conditions for polymerase chain-reaction amplification of ten exon regions (Exons 3, 7, 11 through 13, and 15 through 19) of the collagen COL4A5 gene and four exon regions (Exons 2, and 12 through 14) of the COL4A6 gene were sequenced and established in this study. These Type IV collagen genes contain 51 and 48 exons, respectively. The sequences of these exons were determined in the two genes in 250 male patients with hematuria and suspected Alport syndrome. Seventeen mutations were found in nine of the ten exons studied in the COL4A5 gene in 17 patients, whereas no mutations were identified in COL4A6. One mutation was identical in two patients known to be unrelated. The results indicate that mutations in COL4A5 that leading to renal failure are more frequent than those involved in classic Alport syndrome, and also that mutations in COL4A6 are not likely to cause this disease. Furthermore, mutations in COL4A5 are distributed quite randomly and no "hot spots" were found.

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 collagen type IV nephropathies: From thin basement membrane nephropathy to Alport syndrome

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 323-326 ◽  
Author(s):  
Alenka Vizjak ◽  
Dusan Ferluga
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Mutation Screening ◽  
Glomerular Sclerosis ◽  
Collagen Type Iv ◽  
Dominant Type ◽  
Thin Basement Membrane Nephropathy ◽  
Type Iv

Alport syndrome and thin basement membrane nephropathy are common causes of persistent familial haematuria. They are associated with various mutations in type IV collagen genes. Mutations in genes, coding for ?5 chain of collagen IV, cause X-linked Alport syndrome, whereas mutations in genes for ?3 and ?4 chains can cause the autosomal recessive and autosomal dominant type of Alport syndrome or benign familial haematuria with thin basement membrane nephropathy. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. Few studies of genotype-phenotype correlations in Alport syndrome have shown that various types of mutations may be a significant predictor of the severity of disease. Histopathologic findings in Alport syndrome vary from normal kidney to nonspecific focal segmental and global glomerular sclerosis with characteristic ultrastructural finding of thickening and splitting of the glomerular basement membrane. Thin basement membrane nephropathy is characterized by diffuse thinning of the glomerular basement membrane on an ultrastructural level, while by light microscopy glomeruli are mostly unremarkable. Because of present limitations of mutation screening techniques, kidney biopsy with mandatory ultrastructural analysis and immunohistochemistry examination for type IV collagen ? chains remains a standard approach for establishing diagnosis and determining the mode of transmission of the disease.

scholarly journals Detection of gene mutations by reverse transcription-polymerase chain reaction and direct sequence method in X-linked Alport syndrome

1998 ◽  
Vol 11 (1) ◽  
pp. 69-73
Author(s):  
Yuji Inoue ◽  
Kukiko Noguchi ◽  
Koichi Nakanishi ◽  
Kazumoto Iijima ◽  
Hajime Nakamura ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Reverse Transcription ◽  
Alport Syndrome ◽  
Gene Mutations ◽  
Direct Sequence ◽  
Chain Reaction ◽  
Sequence Method ◽  
Polymerase Chain

IDENTIFICATION OF ??3, ??4, AND ??5 CHAINS OF TYPE IV COLLAGEN AS ALLOANTIGENS FOR ALPORT POSTTRANSPLANT ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODIES

2000 ◽  
Vol 69 (4) ◽  
pp. 679-684 ◽  
Author(s):  
Raghu Kalluri ◽  
Adriana Torre ◽  
Charles F. Shield ◽  
Eric D. Zamborsky ◽  
Michelle C. Werner ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Type Iv

scholarly journals Glomerular Basement Membrane Selective Permeability in Short-term Streptozotocin-induced Diabetic Rats

2000 ◽  
Vol 1 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Michele Doucet ◽  
Irene Londoño ◽  
Amparo Gómez-Pascual ◽  
Moise Bendayan
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Serum Proteins ◽  
Diabetic Rats ◽  
Glomerular Permeability ◽  
Structural Alterations ◽  
Early Stages ◽  
Type Iv ◽  
Basement Membrane Thickening

In diabetes, the glomerular basement membrane undergoes thickening and structural alterations with loss of glomerular permselectivity properties. However, the onset of the alterations at early phases of diabetes is unclear. Aiming to determine the functional and structural alterations of the glomerular wall in the early stages of diabetes, we have studied the distribution of endogenous circulating albumin and type IV collagen in the glomerular basement membrane, using the immunocytochemical approach. The streptozotocin-injected hyperglycemic rat was our animal model. Renal tissues were examined after 10 days, 2, 4 and 6 months of hyperglycemia. Upon immunogold labelings, changes in the glomerular permeability to endogenous albumin were found altered as early as upon ten days of hyperglycemia. In contrast, no structural modifications were detected at this time point. Indeed, glomerular basement membrane thickening and an altered type IV collagen labeling distribution were only observed after four months of hyperglycemia, suggesting that functional alterations take place early in diabetes prior to any structural modification. In order to evaluate the reversibility of the glomerular alterations, two-month-old diabetic animals were treated with insulin. These animals showed a significant restoring of their glomerular permselectivity. Our results suggest a link between glycemic levels and alteration of glomerular permeability in early stages of diabetes, probably through high levels of glycated serum proteins.

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