1/68. Molecular genetic and immunohistochemical study of autosomal recessive Alport's syndrome.A dna analysis of autosomal type IV collagen alpha3 and alpha4 chain genes (COL4A3 and COL4A4) and an immunohistochemical study of type IV collagen alpha1 to alpha6 chains were performed in an inbred family with autosomal recessive Alport's syndrome (AS). A linkage study using polymorphic markers around the COL4A3/COL4A4 genes clearly differentiated the affected patients from healthy individuals. These patients were homozygous for all markers analyzed, whereas their parents were heterozygotes. Because of the large size of both the genes and the heterogeneous range of the mutations of these genes, linkage analysis by using highly polymorphic markers is still the method of choice in genetic counseling for autosomal recessive AS, as well as for the X-linked form. Although the distribution of alpha1 and alpha2 chains in the index patient and her affected sister were normal, the alpha3 and alpha4 chains were completely defective in the renal basement membrane (BM). The alpha5 chain could be found in Bowman's capsular basement membrane (BCBM) but not in the glomerular basement membrane (GBM). In addition, our study showed, for the first time, that the alpha6 chain in BCBM is spared in this form of AS. This abnormal pattern of type IV collagen could be a useful tool for differentiation of the autosomal recessive type from the X-linked type of AS.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
2/68. Coexistence of thin membrane and alport nephropathies in families with haematuria.The finding of familial haematuria without a history of deafness or renal impairment is often assumed to indicate a benign prognosis. However, we describe three families in whom Alport and thin basement membrane nephropathy were separately identified within the same pedigree. Our findings illustrate the importance of fully investigating families with haematuria, even if thin basement nephropathy has been diagnosed in one member.- - - - - - - - - - ranking = 1.6666666666667keywords = membrane (Clic here for more details about this article) |
3/68. rupture of the anterior lens capsule in Alport syndrome.Alport syndrome is an inherited disorder of type IV collagen, a major constituent of basement membranes. Eighty-five percent of cases are transmitted through X-linked dominant inheritance, although autosomal dominant and autosomal recessive inheritance has also been reported. Clinical manifestations of Alport syndrome include progressive glomerulopathy, sensorineural deafness, anterior lenticonus, posterior corneal dystrophy, and abnormal retinal pigmentation. Anterior lenticonus may lead to loss of vision because of progressive myopia or cataract formation. We report 2 cases of unusual cataract formation in adolescent boys who had a rupture of the anterior lens capsule. One rupture was spontaneous, and the other was traumatic.- - - - - - - - - - ranking = 0.33333333333333keywords = membrane (Clic here for more details about this article) |
4/68. Bilateral anterior lenticonus: Scheimpflug imaging system documentation and ultrastructural confirmation of Alport syndrome in the lens capsule.BACKGROUND: Alport syndrome is a combination of proteinuria, hematuria, and neurosensory high-frequency deafness. Bilateral anterior lenticonus may be a late sign. diagnosis relies on characteristic electron microscopy changes of glomerular basement membranes in renal biopsy specimens. PATIENT: A 38-year-old man was seen for progressive visual acuity loss (20/400 OU; best-corrected visual acuity, 20/60 OD and 20/50 OS). Findings from slitlamp examination included bilateral anterior lenticonus and central posterior subcapsular cataract, documented using a modified Scheimpflug imaging system. Retinal pathology was not present. On detailed questioning, a history of microhematuria and proteinuria since childhood and progressive high-frequency deafness for years were discovered. The family history was negative for nephropathies, deafness, or eye diseases. cataract extraction rehabilitated the patient's vision. RESULTS: Electron microscopy of a fragile capsulorhexis specimen showed typical thinned basal lamina with basement membrane disruptions. CONCLUSIONS: Anterior lenticonus is a rare bilateral progressive developmental anomaly. More than 90% of cases are associated with Alport syndrome. For diagnosis of Alport syndrome, the presence of 3 of 4 criteria is required: family history positive for Alport syndrome, progressive intra-auricular deafness, characteristic eye anomalies, and positive findings from glomerular ultrastructural examination. We believe that ultrastructural proof of anterior lenticonus may also be provided in the lens capsule. Arch Ophthalmol. 2000;118:895-897- - - - - - - - - - ranking = 0.66666666666667keywords = membrane (Clic here for more details about this article) |
5/68. Sporadic case of X-chromosomal Alport syndrome in a consanguineous family.Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematuria and progressive nephropathy leading to renal failure. The main extrarenal features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected families, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who presented with an unusual association of obstructive uropathy and AS. hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after medical treatment of poststreptococcal GN and surgical correction of obstructive uropathy finally led to renal biopsy. The observed ultrastructural changes of the glomerular basement membrane were typical for AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the value of molecular studies for genetic counselling in AS.- - - - - - - - - - ranking = 0.66666666666667keywords = membrane (Clic here for more details about this article) |
6/68. Alport-like glomerular changes in a patient with nephrotic syndrome: report of a case.We report a 17-year-old Saudi girl who presented with nephrotic syndrome at the age of 7 years. A renal biopsy revealed a mildly proliferative immune complex-mediated glomerulonephritis, which on ultrastructural examination revealed prominent thickening of the capillary basement membranes, along with marked splitting and lamellation of lamina densa resembling those seen in Alport syndrome. These changes were even more pronounced in renal biopsies performed 1 and 3 years later, respectively. Thorough clinical evaluations and follow-up of more than 10 years failed to reveal any evidence of Alport syndrome. review of the literature revealed four similar cases reported previously. Diffuse and prominent Alport-like glomerular changes may rarely be seen in patients with nephrotic syndrome in the absence of Alport syndrome. Pathogenesis of these changes, however, remains to be understood.- - - - - - - - - - ranking = 0.33333333333333keywords = membrane (Clic here for more details about this article) |
7/68. Familial interstitial nephritis with progressive renal failure.We describe a 53-year-old woman with chronic interstitial nephritis and asymptomatic impairment of renal function. Seven members of her family were suffering from renal failure and underwent hemodialysis. At the time of their hospital admissions, they had shown evidence of end-stage renal failure at 40 to 50 years of age. Lack of proteinuria, hematuria, hypertension, hyperuricemia, hearing loss, and visual impairment were present before the deterioration of the renal function. Renal biopsy of the presented case indicated chronic interstitial nephritis without glomerular basement membrane abnormalities. Progressive decline of renal function and the inheritance pattern of autosomal dominance in this family suggested the diagnosis of familial interstitial nephritis.- - - - - - - - - - ranking = 0.33333333333333keywords = membrane (Clic here for more details about this article) |
8/68. Ruptured intracranial aneurysm in an adolescent with Alport's syndrome--a new expression of type IV collagenopathy: case report.BACKGROUND: Aneurysmal subarachnoid hemorrhage is uncommon in the pediatric and adolescent age groups. Collagenopathies, particularly of collagen type iii and IV, have been recognized in the pathogenesis of intracranial (i.c.) aneurysms in recent studies of cerebrovascular immunoreactivity and the molecular architecture of the walls of cerebral blood vessels. Alport's syndrome is a genetic disease characterized by imperfect synthesis of type IV collagen leading to sensorineural hearing loss and hematuria. The hematuria results from an abnormal synthesis of the type IV collagen of the glomerular basement membrane. CASE DESCRIPTION: After a motor vehicle accident, this 14-year-old male driver presented with diffuse subarachnoid hemorrhage confirmed by computerized tomography. Subsequent cerebral angiography revealed a left carotid artery bifurcation aneurysm. A retrospective review of the patient's history disclosed renal biopsy-proven hereditary Alport's syndrome. The patient underwent left pterional craniotomy and clipping of the aneurysm, which had clearly ruptured. CONCLUSIONS: The authors present the first clinical observation of a ruptured cerebral aneurysm in an adolescent male with Alport's syndrome. In this case the type IV collagenopathy of Alport's syndrome may have contributed to the genesis of this adolescent's aneurysm. Intracranial aneurysms may be more common in the population of collagenopathies than previously suspected and non-invasive screening may be appropriate.- - - - - - - - - - ranking = 0.33333333333333keywords = membrane (Clic here for more details about this article) |
9/68. Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation.BACKGROUND: Alport syndrome (AS) is a clinically and genetically heterogeneous renal disorder, predominantly affecting the type IV collagen alpha 3/alpha 4/alpha 5 network of the glomerular basement membrane (GBM). AS can be caused by mutations in any of the three genes encoding these type IV collagen chains. The majority of AS families (85%) are X-linked (XL-AS) involving mutations in the COL4A5 gene. Mutations in the COL4A3 and COL4A4 genes cause autosomal recessive AS (AR-AS), accounting for approximately 14% of the cases. Recently, autosomal dominant AS (AD-AS) was linked to the COL4A3/COL4A4 locus in a large family. methods: COL4A3 and COL4A4 cDNAs were generated by nested reverse transcription-polymerase chain reaction and were analyzed by dna sequence analysis. Denaturating high-performance liquid chromatography (DHPLC) was used for mutation and segregation analysis at the genomic dna level. RESULTS: In the AD-AS family, a splice site mutation resulting in skipping of exon 21 of the COL4A3 gene was detected. The mutation does not alter the reading frame and is predicted to result in a COL4A3 chain with an internal deletion. CONCLUSION: As the NC domain is intact, this chain may be incorporated and distort the collagen triple helix, thereby causing the dominant effect of the mutation. The finding of a specific COL4A3 mutation in AD-AS completes the spectrum of type IV collagen mutations in all genetic forms of AS.- - - - - - - - - - ranking = 0.33333333333333keywords = membrane (Clic here for more details about this article) |
10/68. Approach to the diagnosis of thin basement membrane nephropathy in females with the use of antibodies to type IV collagen.CONTEXT: Thin basement membrane nephropathy is recognized by a diffusely thin glomerular basement membrane (GBM) ultrastructurally. In contrast to Alport syndrome (AS), there is no GBM thickening, lamellation, or granular inclusions. Morphologically, there is overlap between thin basement membrane nephropathy and AS in female patients in whom there might be only thin GBM and no pathognomonic findings of AS. OBJECTIVE: To determine if the use of antibodies to collagen IV is helpful in making the distinction between thin basement membrane nephropathy and AS in female patients with primarily thin GBMs. DESIGN: We examined renal biopsies from 9 adult female patients with thin GBMs for the presence of alpha1, alpha3, alpha4, and alpha5 chains of type IV collagen by immunofluorescence. RESULTS: In 2 patients with segmental GBM staining, no suggestion for AS was found on physical examination or in their family history. In the remaining 7 patients with normal GBM staining, 4 had family members with end-stage renal disease of unknown etiology, raising the suspicion of X-linked or autosomal-recessive AS. Three patients were presumed to have thin basement membrane nephropathy. CONCLUSION: Segmental GBM staining for alpha3, alpha4, and alpha5 chains of type IV collagen raises the suspicion of AS in the presence of adequate controls and other supporting evidence. Normal GBM staining for alpha3, alpha4, and alpha5 chains of type IV collagen, however, does not exclude AS.- - - - - - - - - - ranking = 3keywords = membrane (Clic here for more details about this article) |
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