Severe Polycystic Liver Disease Is Not Caused by Large Deletions of the PRKCSH Gene.
| Autor: | Cnossen WR; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands., Maurits JS; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands., Salomon J; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.; Laboratory of Gastroenterology and Hepatology, ADPLD Diagnostics, Radboud University Medical Center, Nijmegen, The Netherlands., Te Morsche RH; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.; Laboratory of Gastroenterology and Hepatology, ADPLD Diagnostics, Radboud University Medical Center, Nijmegen, The Netherlands., Waanders E; Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Drenth JP; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. joostphdrenth@cs.com. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of clinical laboratory analysis [J Clin Lab Anal] 2016 Sep; Vol. 30 (5), pp. 431-6. Date of Electronic Publication: 2015 Sep 13. |
| DOI: | 10.1002/jcla.21875 |
| Abstrakt: | Background: Isolated polycystic liver disease (ADPLD) is an autosomal dominant Mendelian disorder. Heterozygous PRKCSH (where PRKCSH is protein kinase C substrate 80K-H (80 kDa protein, heavy chain; MIM*177060) mutations are the most frequent cause. Routine molecular testing using Sanger sequencing identifies pathogenic variants in the PRKCSH (15%) and SEC63 (where SEC63 is Saccharomyces cerevisiae homolog 63 (MIM*608648); 6%) genes, but about approximately 80% of patients meeting the clinical ADPLD criteria carry no PRKCSH or SEC63 mutation. Cyst tissue often shows somatic deletions with loss of heterozygosity that was recently recognized as a general mechanism in ADPLD. We hypothesized that germline deletions in the PRKCSH gene may be responsible for hepatic cystogenesis in a significant number of mutation-negative ADPLD patients. Methods: In this study, we designed a multiplex ligation-dependent probe amplification (MLPA) assay to screen for deletions of PRKCSH exons. Genomic DNA from 60 patients with an ADPLD phenotype was included. Results: MLPA analysis detected no exon deletions in mutation-negative ADPLD patients. Conclusion: Large copy number variations on germline level are not present in patients with a clinical diagnosis of ADPLD. MLPA analysis of the PRKCSH gene should not be considered as a diagnostic method to explain hepatic cystogenesis. (© 2015 Wiley Periodicals, Inc.) |
| Databáze: | MEDLINE |
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