{"doi":"10.1016/j.ekir.2020.01.009","title":"Large Deletions in GANAB and SEC63 Explain 2 Cases of Polycystic Kidney and Liver Disease","abstract":"See Commentary on Page 575 See Commentary on Page 575 Autosomal dominant polycystic kidney disease (ADPKD) is caused by loss-of-function or deleterious mutations in the PKD1 or PKD2 genes and is seen with a prevalence of 1:400 to 1:1000.1Torres V.E. Harris P.C. Pirson Y. Autosomal dominant polycystic kidney disease.Lancet. 2007; 369: 1287-1301Abstract Full Text Full Text PDF PubMed Scopus (909) Google Scholar Patients develop kidney and liver cysts that accumulate and expand to crowd out the normal organ parenchyma and lead to kidney failure in half of patients by age 60 years.2Harris P.C. Torres V.E. Polycystic kidney disease.Annu Rev Med. 2009; 60: 321-337Crossref PubMed Scopus (537) Google Scholar To find targeted therapies, we need to better understand the function of the PKD1 and PKD2 gene products, polycystin-1 (PC1) and polycystin-2 (PC2). Autosomal dominant polycystic liver disease (ADPLD), also known as isolated polycystic liver disease (PCLD), is a clinical characterization of patients on the same phenotypic and mechanistic spectrum as ADPKD with regard to their liver cysts, but lacking clinically relevant kidney cysts.3Qian Q. Li A. King B.F. et al.Clinical profile of autosomal dominant polycystic liver disease.Hepatology. 2003; 37: 164-171Crossref PubMed Scopus (160) Google Scholar Autopsy studies suggest that PCLD has a similar prevalence to that of ADPKD.4Besse W. Dong K. Choi J. et al.Isolated polycystic liver disease genes define effectors of polycystin-1 function.J Clin Invest. 2017; 127: 3558Crossref PubMed Scopus (15) Google Scholar Approximately 50% of cases of this phenotype have been explained by mutations in any 1 of at least 7 endoplasmic reticulum protein-encoding genes, the loss of which indirectly results in insufficient PC1 functional dosage.4Besse W. Dong K. Choi J. et al.Isolated polycystic liver disease genes define effectors of polycystin-1 function.J Clin Invest. 2017; 127: 3558Crossref PubMed Scopus (15) Google Scholar, 5Fedeles S.V. Tian X. Gallagher A.R. et al.A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation.Nat Genet. 2011; 43: 639-647Crossref PubMed Scopus (153) Google Scholar, 6Cornec-Le Gall E. Torres V.E. Harris P.C. Genetic complexity of autosomal dominant polycystic kidney and liver diseases.J Am Soc Nephrol. 2018; 29: 13-23Crossref PubMed Scopus (88) Google Scholar These genes include PRKCSH, SEC63, GANAB, ALG8, SEC61B, DNAJB11, and ALG9.6Cornec-Le Gall E. Torres V.E. Harris P.C. Genetic complexity of autosomal dominant polycystic kidney and liver diseases.J Am Soc Nephrol. 2018; 29: 13-23Crossref PubMed Scopus (88) Google Scholar Variants in GANAB, DNAJB11, and ALG9 explain a small number of cases clinically suspected to have ADPKD.6Cornec-Le Gall E. Torres V.E. Harris P.C. Genetic complexity of autosomal dominant polycystic kidney and liver diseases.J Am Soc Nephrol. 2018; 29: 13-23Crossref PubMed Scopus (88) Google Scholar,7Besse W. Chang A.R. Luo J.Z. et al.ALG9 mutation carriers develop kidney and liver cysts.J Am Soc Nephrol. 2019; 30: 2091-2102Crossref PubMed Scopus (24) Google Scholar We aim to solve additional cases by improving the sensitivity of variant identification in established genes, and through implication of novel disease genes. These genes will be potential targets for treatments to upregulate the functional dosage of PC1. Whole exome sequencing (WES) is a useful technique for gene discovery projects, as it sequences the coding regions and flanking intronic bases of all defined genes regardless of their implicated role in human homeostasis or disease.8Bamshad M.J. Ng S.B. Bigham A.W. et al.Exome sequencing as a tool for Mendelian disease gene discovery.Nat Rev Genet. 2011; 12: 745-755Crossref PubMed Scopus (1182) Google Scholar WES is highly sensitive at identifying small insertions, deletions, and single- or oligo-nucleotide variants. Because of its 75−base","journal":"Kidney International Reports","year":2020,"id":73152,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9407,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333799,"name":"Jungmin Choi","orcid":"0000-0002-8614-0973","position":1,"is_corresponding":false},{"id":232142,"name":"Vicente E. Torres","orcid":"0000-0003-2008-1576","position":2,"is_corresponding":false},{"id":385213,"name":"Stefan Somlo","orcid":"0000-0001-5062-4629","position":3,"is_corresponding":false},{"id":385214,"name":"Whitney Besse","orcid":"0000-0002-8283-1507","position":4,"is_corresponding":false},{"id":385212,"name":"Elena Wilson","orcid":"0000-0002-4139-2018","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T21:45:32.034078Z","pmid":"32405593","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}