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Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992149/ https://www.ncbi.nlm.nih.gov/pubmed/24694054 http://dx.doi.org/10.1186/1471-2350-15-41 |
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author | Obeidova, Lena Elisakova, Veronika Stekrova, Jitka Reiterova, Jana Merta, Miroslav Tesar, Vladimir Losan, Frantisek Kohoutova, Milada |
author_facet | Obeidova, Lena Elisakova, Veronika Stekrova, Jitka Reiterova, Jana Merta, Miroslav Tesar, Vladimir Losan, Frantisek Kohoutova, Milada |
author_sort | Obeidova, Lena |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3992149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39921492014-04-20 Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease Obeidova, Lena Elisakova, Veronika Stekrova, Jitka Reiterova, Jana Merta, Miroslav Tesar, Vladimir Losan, Frantisek Kohoutova, Milada BMC Med Genet Research Article 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. BioMed Central 2014-04-03 /pmc/articles/PMC3992149/ /pubmed/24694054 http://dx.doi.org/10.1186/1471-2350-15-41 Text en Copyright © 2014 Obeidova et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Research Article Obeidova, Lena Elisakova, Veronika Stekrova, Jitka Reiterova, Jana Merta, Miroslav Tesar, Vladimir Losan, Frantisek Kohoutova, Milada Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease |
title | Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease |
title_full | Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease |
title_fullStr | Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease |
title_full_unstemmed | Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease |
title_short | Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease |
title_sort | novel mutations of pkd genes in the czech population with autosomal dominant polycystic kidney disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992149/ https://www.ncbi.nlm.nih.gov/pubmed/24694054 http://dx.doi.org/10.1186/1471-2350-15-41 |
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