Location of mutations within the PKD2 gene influences clinical outcome
| Autor: | Saturnino Sanz de Castro, Nadja Bogdanova, Dimitrakov D, Roser Torra, Isabel Martínez, Ali R. Afzal, Jose L. San-Millan, Dorien J.M. Peters, Steve Jeffery, David Ravine, Barbera Veldhuisen, Eliecer Coto, Nick Hateboer, A K Saggar-Malik, Marjan A. van Dijk, Michael Krawczak, Martijn H. Breuning |
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| Rok vydání: | 2000 |
| Předmět: |
Male
TRPP Cation Channels Genotype PKD2 DNA Mutational Analysis Autosomal dominant polycystic kidney disease Gene mutation Biology medicine.disease_cause urologic and male genital diseases Severity of Illness Index Genotype-phenotype distinction autosomal dominant medicine Polycystic kidney disease inherited kidney disease Humans gene mutation Gene Genetics Mutation Analysis of Variance polycystic kidney disease Chromosome Mapping Membrane Proteins medicine.disease Polycystic Kidney Autosomal Dominant Phenotype Nonlinear Dynamics Nephrology Regression Analysis Female |
| Zdroj: | Kidney international. 57(4) |
| ISSN: | 0085-2538 |
| Popis: | Location of mutations within the PKD2 gene influences clinical outcome. Background Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. Methods Detailed clinical information was collected for PKD2 families in which the underlying mutation had been identified. Logistic regression analysis was employed to assess the influence of age and sex on hypertension, hematuria, renal calculi, and urinary tract infections, and a clinical phenotype score was computed. Patients were then grouped according to the relative location of their mutation within the cDNA sequence, and differences in the mean phenotypic score between groups were tested for statistical significance by means of a multiple pairwise t-test. Results While phenotypic scores for each mutational group revealed a considerable degree of intragroup variability, the variability in phenotypic scores was significantly higher between mutational groups than within groups. A group-wise comparison of the mean phenotypic scores confirmed the observation of significant nonlinear variation in disease severity, with high- and low-scoring mutational groups interspersed along the gene sequence. Conclusion The identification of groups of mutations in the PKD2 gene, which differ significantly with respect to clinical outcome, is to our knowledge the first description of a genotype/phenotype correlation in autosomal dominant polycystic kidney disease. It also provides evidence against complete loss of function of the mutant PKD2 gene product. |
| Databáze: | OpenAIRE |
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