COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy
| Autor: | Voskarides, Konstantinos, Damianou, Loukas, Neocleous, Vassos, Zouvani, Ioanna, Christodoulidou, Stalo, Hadjiconstantinou, Valsamakis E., Ioannou, Kyriakos, Athanasiou, Yiannis, Patsias, Charalambos, Alexopoulos, Efstathios, Pierides, Alkis M., Kyriacou, Kyriacos C., Constantinou-Deltas, Constantinos D. |
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| Přispěvatelé: | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] |
| Rok vydání: | 2007 |
| Předmět: |
Nephrology
Male Pathology Genetic Linkage kidney disease urologic and male genital diseases Autoantigens Cohort Studies Type IV collagen Focal segmental glomerulosclerosis Glomerular Basement Membrane gene mutation Glomerulosclerosis Focal Segmental adult article Linkage (Genetics) Glomerulonephritis General Medicine Middle Aged Founder Effect Pedigree medicine.anatomical_structure female founder effect priority journal col4a3 gene Female focal glomerulosclerosis Adult Collagen Type IV medicine.medical_specialty col4a4 gene gene locus kidney biopsy DNA sequence Nephropathy male Internal medicine medicine Humans controlled study human gene Hematuria gelatinase A Basement membrane business.industry medicine.disease basement membrane human tissue kidney failure hematuria Cyprus Mutation Kidney Failure Chronic CFHR5 nephropathy proteinuria business genetic predisposition Kidney disease |
| Zdroj: | Journal of the American Society of Nephrology J.Am.Soc.Nephrol. |
| Popis: | Mutations in the COL4A3/COL4A4 genes of type IV collagen have been found in ∼40% of cases of thin basement membrane nephropathy, which is characterized by microscopic hematuria and is classically thought to cause proteinuria and chronic renal failure rarely. Here we report our observations of 116 subjects from 13 Cypriot families clinically affected with thin basement membrane nephropathy. These families first came to our attention because they segregated microscopic hematuria, mild proteinuria, and variable degrees of renal impairment, but a dual diagnosis of focal segmental glomerulosclerosis (FSGS) and thin basement membrane nephropathy was made in 20 biopsied cases. Molecular studies identified founder mutations in both COL4A3 and COL4A4 genes in 10 families. None of 82 heterozygous patients had any extrarenal manifestations, supporting the diagnosis of thin basement membrane nephropathy. During follow-up of up to three decades, 31 of these 82 patients (37.8%) developed chronic renal failure and 16 (19.5%) reached end-stage renal disease. Mutations G1334E and G871C were detected in seven and three families, respectively, and were probably introduced by founders. We conclude that these particular COL4A3/COL4A4 mutations either predispose some patients to FSGS and chronic renal failure, or that thin basement membrane nephropathy sometimes coexists with another genetic modifier that is responsible for FSGS and progressive renal failure. The findings presented here do not justify the labelling of thin basement membrane nephropathy as a benign condition with excellent prognosis. Copyright © 2007 by the American Society of Nephrology. 18 3004 3016 Cited By :82 |
| Databáze: | OpenAIRE |
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