Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease
| Autor: | M Merta, Frantisek Losan, Lena Obeidova, Vladimir Tesar, Milada Kohoutová, Veronika Elisakova, Reiterová J, Jitka Stekrova |
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| Rok vydání: | 2014 |
| Předmět: |
Male
TRPP Cation Channels Genetic Linkage Population Autosomal dominant polycystic kidney disease PKD gene Biology urologic and male genital diseases medicine.disease_cause Polymerase Chain Reaction High Resolution Melt Cohort Studies Polycystic kidney disease Genetic linkage Genetics medicine Humans Transition Temperature Genetics(clinical) Genetic Testing Multiplex ligation-dependent probe amplification education Genetics (clinical) ADPKD Czech Republic education.field_of_study Mutation PKD1 urogenital system Sequence Analysis DNA Mutational analysis Polycystic Kidney Autosomal Dominant medicine.disease Molecular biology female genital diseases and pregnancy complications MLPA Female Multiplex Polymerase Chain Reaction HRM Research Article |
| Zdroj: | BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/1471-2350-15-41 |
| Popis: | Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder caused by mutation in either one of two genes, PKD1 and PKD2. High structural and sequence complexity of PKD genes makes the mutational diagnostics of ADPKD challenging. The present study is the first detailed analysis of both PKD genes in a cohort of Czech patients with ADPKD using High Resolution Melting analysis (HRM) and Multiplex Ligation-dependent Probe Amplification (MLPA). Methods The mutational analysis of PKD genes was performed in a set of 56 unrelated patients. For mutational screening of the PKD1 gene, the long-range PCR (LR-PCR) strategy followed by nested PCR was used. Resulting PCR fragments were analyzed by HRM; the positive cases were reanalyzed and confirmed by direct sequencing. Negative samples were further examined for sequence changes in the PKD2 gene by the method of HRM and for large rearrangements of both PKD1 and PKD2 genes by MLPA. Results Screening of the PKD1 gene revealed 36 different likely pathogenic germline sequence changes in 37 unrelated families/individuals. Twenty-five of these sequence changes were described for the first time. Moreover, a novel large deletion was found within the PKD1 gene in one patient. Via the mutational analysis of the PKD2 gene, two additional likely pathogenic mutations were detected. Conclusions Probable pathogenic mutation was detected in 71% of screened patients. Determination of PKD mutations and their type and localization within corresponding genes could help to assess clinical prognosis of ADPKD patients and has major benefit for prenatal and/or presymptomatic or preimplantational diagnostics in affected families as well. |
| Databáze: | OpenAIRE |
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