ArticlePloS one2012
Loss of heterozygosity is present in SEC63 germline carriers with polycystic liver disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.Science translational medicine · 2023Article
- Article
- Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- Is Nucleoredoxin a Master Regulator of Cellular Redox Homeostasis? Its Implication in Different Pathologies.Antioxidants (Basel, Switzerland) · 2022Review
- Volleying plasma membrane proteins from birth to death: Role of J-domain proteins.Frontiers in molecular biosciences · 2022Review
- Molecular Mechanisms of Isolated Polycystic Liver Diseases.Frontiers in genetics · 2022Review
- Emerging View on the Molecular Functions of Sec62 and Sec63 in Protein Translocation.International journal of molecular sciences · 2021Review
- Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases.Nature reviews. Gastroenterology & hepatology · 2019Review
- Therapeutic Targets in Polycystic Liver Disease.Current drug targets · 2017Review
- Chromosomal abnormalities in hepatic cysts point to novel polycystic liver disease genes.European journal of human genetics : EJHG · 2016Article
- Severe Polycystic Liver Disease Is Not Caused by Large Deletions of the PRKCSH Gene.Journal of clinical laboratory analysis · 2016Article
- Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity.The Journal of clinical investigation · 2015Article
- Polycystic liver diseases: advanced insights into the molecular mechanisms.Nature reviews. Gastroenterology & hepatology · 2014Review
- Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management.Orphanet journal of rare diseases · 2014Review
- Polycystin-1: a master regulator of intersecting cystic pathways.Trends in molecular medicine · 2014Review
- Hepatic loss of miR-122 predisposes mice to hepatobiliary cyst and hepatocellular carcinoma upon diethylnitrosamine exposure.The American journal of pathology · 2013Article
- Rare cystic liver lesions: a diagnostic and managing challenge.World journal of gastroenterology · 2013Review
- Let's talk about Secs: Sec61, Sec62 and Sec63 in signal transduction, oncology and personalized medicine.Signal transduction and targeted therapyReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycystic liver disease (PCLD) is an autosomal dominant disorder characterised by multiple fluid filled cysts in the liver. This rare disease is caused by heterozygous germline mutations in PRKCSH and SEC63. We previously found that, in patients with a PRKCSH mutation, over 76% of the cysts acquired a somatic 'second-hit' mutation in the wild type PRKCSH allele. We hypothesise that somatic second-hit mutations are a general mechanism of cyst formation in PCLD which also plays a role in PCLD patients carrying a SEC63 germline mutation. We collected cyst epithelial cells from 52 liver cysts from three different SEC63 patients using laser microdissection. DNA samples were sequenced to identify loss of heterozygosity (LOH) mutations and other somatic mutations in cyst epithelial DNA. We discovered somatic SEC63 mutations in patient 3 (1/14 cysts), but not in patient 1 and 2 (38 cysts). Upon review we found that the germline mutation of patient 1 and 2 (SEC63 c.1703_1705delAAG) was present in the same frequency in DNA samples from healthy controls, suggesting that this variant is not causative of PCLD. In conclusion, as somatic second-hit mutations also play a role in cyst formation in patients with a SEC63 germline mutation, this appears to be a general mechanism of cyst formation in PCLD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.