{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:47:33Z","timestamp":1783435653298,"version":"3.54.6"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is mainly characterized by renal involvement with progressive bilateral development of renal cysts and volumetric increase in the kidneys, causing a loss of renal function, chronic kidney disease (CKD), and kidney failure. The occurrence of mosaicism may modulate the clinical course of the disease. Mosaicism is characterized by a few cell populations with different genomes. In these special cases, a genetic diagnosis could be challenging. Methods: Herein, we describe the case of a 47-year-old woman presenting with typical ultrasound and computed tomography features of ADPKD. She had stage 3b CKD and hypertension. There was no family history of ADPKD, prompting an investigation with a genetic test. Target next-generation sequencing (NGS) did not detect the presence of any genomic variants. Therefore, we carried out second-level genetic analysis to investigate the presence of a large rearrangement through a multiple ligation-dependent probe amplification (MLPA) analysis of PKD1 and PKD2 genes. Results: MLPA showed a large deletion (portion including exons 2\u201334 of PKD1) present in the heterozygosis with a percentage of cells close to the resolution limits of the technique used (&lt;25\u201330%). We concluded that the large deletion identified was mosaicism. This variant is not reported in major ADPKD databases, but due to the type of mutation and the patient\u2019s clinical picture, it should be considered as likely pathogenic. Conclusions: A stepwise genetic approach might be useful in those cases where standard methods do not allow one to reach a definitive diagnosis.<\/jats:p>","DOI":"10.3390\/genes16010039","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:26:25Z","timestamp":1735651585000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Typical Clinical Presentation of an Autosomal Dominant Polycystic Kidney Disease Patient with an Atypical Genetic Pattern"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9225-4036","authenticated-orcid":false,"given":"Nenzi","family":"Marzano","sequence":"first","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6945-4460","authenticated-orcid":false,"given":"Carlotta","family":"Caprara","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Nephrology, Dialysis and Transplantation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Medical Genetics and Genomics, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-117X","authenticated-orcid":false,"given":"Thiago","family":"Reis","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Bras\u00edlia, Bras\u00edlia 70910-900, Brazil"},{"name":"Fenix Nephrology, S\u00e3o Paulo 04508-011, Brazil"},{"name":"Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Montin","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Health Sciences, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Pretto","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-9368","authenticated-orcid":false,"given":"Matteo","family":"Rigato","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Nephrology, Dialysis and Transplantation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Gastaldon","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7000-4907","authenticated-orcid":false,"given":"Barbara","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-4065","authenticated-orcid":false,"given":"Claudio","family":"Ronco","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Zanella","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Nephrology, Dialysis and Transplantation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-6715","authenticated-orcid":false,"given":"Daniela","family":"Zuccarello","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Corradi","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Nephrology, Dialysis and Transplantation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1056\/NEJMra1010172","article-title":"Ciliopathies","volume":"364","author":"Hildebrandt","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"Burgmaier, K., Gimpel, C., Schaefer, F., and Liebau, M. (1993). Autosomal Recessive Polycystic Kidney Disease\u2014PKHD1, University of Washington."},{"key":"ref_3","first-page":"655","article-title":"Studio epidemiologico e molecolare sulla malattia autosomica dominante del rene policistico (adpkd) nella provincia di vicenza: Possibile effetto fondatore? Epidemiological and Molecular Study of Autosomal Dominant Polycystic Kidney Disease (Adpkd) in the Province of Vicenza (a Region of North Eastern Italy): A Founder Effect?","volume":"27","author":"Corradi","year":"2010","journal-title":"G. Ital. Nefrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e0190430","DOI":"10.1371\/journal.pone.0190430","article-title":"The Prevalence of Autosomal Dominant Polycystic Kidney Disease (ADPKD): A Meta-Analysis of European Literature and Prevalence Evaluation in the Italian Province of Modena Suggest That ADPKD Is a Rare and Underdiagnosed Condition","volume":"13","author":"Solazzo","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.5414\/CNP72259","article-title":"Clinical Pattern of Adult Polycystic Kidney Disease in a Northeastern Region of Italy","volume":"72","author":"Corradi","year":"2009","journal-title":"Clin. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.23736\/S0026-4806.16.04830-8","article-title":"Predictors of Rapid Disease Progression in Autosomal Dominant Polycystic Kidney Disease","volume":"108","author":"Corradi","year":"2017","journal-title":"Minerva Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1681\/ASN.2008050507","article-title":"Unified Criteria for Ultrasonographic Diagnosis of ADPKD","volume":"20","author":"Pei","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jdiaa, S.S., Mustafa, R.A., and Yu, A.S.L. (2024). Treatment of Autosomal Dominant Polycystic Kidney Disease. Am. J. Kidney Dis., in press.","DOI":"10.1053\/j.ajkd.2024.08.008"},{"key":"ref_9","first-page":"9","article-title":"Slowing Progression of Chronic Kidney Disease in Polycistic Kidney Disease Patients with Tolvaptan: From Guidelines to Clinical Practice","volume":"5","author":"Giuliani","year":"2021","journal-title":"G. Ital. Nefrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1053\/j.ajkd.2008.05.015","article-title":"Presence of De Novo Mutations in Autosomal Dominant Polycystic Kidney Disease Patients Without Family History","volume":"52","author":"Reed","year":"2008","journal-title":"Am. J. Kidney Dis."},{"key":"ref_11","first-page":"1724","article-title":"Genetica e Counseling Genetico","volume":"33","author":"Claudia","year":"2016","journal-title":"G. Ital. Nefrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.ajhg.2016.05.004","article-title":"Mutations in GANAB, Encoding the Glucosidase II\u03b1 Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease","volume":"98","author":"Porath","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.ajhg.2018.03.013","article-title":"Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease","volume":"102","author":"Olson","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.kint.2020.02.022","article-title":"Clinical Spectrum, Prognosis and Estimated Prevalence of DNAJB11-Kidney Disease","volume":"98","author":"Huynh","year":"2020","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ajhg.2021.11.016","article-title":"Monoallelic IFT140 Pathogenic Variants Are an Important Cause of the Autosomal Dominant Polycystic Kidney-Spectrum Phenotype","volume":"109","author":"Senum","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.ajhg.2022.06.013","article-title":"Monoallelic Pathogenic ALG5 Variants Cause Atypical Polycystic Kidney Disease and Interstitial Fibrosis","volume":"109","author":"Lemoine","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1681\/ASN.2019030298","article-title":"ALG9 Mutation Carriers Develop Kidney and Liver Cysts","volume":"30","author":"Besse","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_18","unstructured":"Adam, M.P., Feldman, J., and Mirzaa, G.M. (2024, November 20). Polycystic Kidney Disease, Autosomal Dominant, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/nbk1246\/."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0140-6736(98)03495-3","article-title":"Comparison of Phonotypes of Polycystic Kidney Disease Types 1 and 2","volume":"353","author":"Hateboer","year":"1999","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1681\/ASN.2006121387","article-title":"Comprehensive Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease","volume":"18","author":"Rossetti","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1053\/j.ajkd.2017.01.046","article-title":"PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis","volume":"70","author":"Renaudineau","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1681\/ASN.2015060648","article-title":"Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease","volume":"27","author":"Hwang","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","first-page":"gin\/33.2.3","article-title":"Clinical Diagnosis of Autosomal Dominant Polycystic Kidney Disease","volume":"33","author":"Magistroni","year":"2016","journal-title":"G. Ital. Nefrol."},{"key":"ref_24","first-page":"gin\/33.5.16.","article-title":"Linee guida per la malattia policistica renale dell\u2019adulto adpkd: Diagnosi Molecolare","volume":"33","author":"Scolari","year":"2016","journal-title":"G. Ital. Nefrol."},{"key":"ref_25","first-page":"S37","article-title":"Rene Policistico: Dall\u2019ereditariet\u00e0 Complessa Alla Terapia","volume":"45","author":"Caprara","year":"2021","journal-title":"Biochim. Clin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jmoldx.2013.10.005","article-title":"Molecular Diagnosis of Autosomal Dominant Polycystic Kidney Disease Using Next-Generation Sequencing","volume":"16","author":"Tan","year":"2014","journal-title":"J. Mol. Diagn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.gene.2012.12.060","article-title":"Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease by Targeted Capture and Next-Generation Sequencing: Utility and Limitations","volume":"516","author":"Qi","year":"2013","journal-title":"Gene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"600","DOI":"10.34172\/aim.2022.95","article-title":"Targeted Next Generation Sequencing Revealed Novel Variants in the PKD1 and PKD2 Genes of Iranian Patients with Autosomal Dominant Polycystic Kidney Disease","volume":"25","author":"Hosseinpour","year":"2022","journal-title":"Arch. Iran. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-genet-041720-093403","article-title":"Mosaicism in Human Health and Disease","volume":"54","author":"Thorpe","year":"2020","journal-title":"Annu. Rev. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.3390\/genes5041064","article-title":"Somatic Mosaicism in the Human Genome","volume":"5","author":"Freed","year":"2014","journal-title":"Genes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.kint.2019.08.038","article-title":"Detection and Characterization of Mosaicism in Autosomal Dominant Polycystic Kidney Disease","volume":"97","author":"Hopp","year":"2020","journal-title":"Kidney Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41439-024-00273-0","article-title":"End-Stage ADPKD with a Low-Frequency PKD1 Mosaic Variant Accelerated by Chemoradiotherapy","volume":"11","author":"Hanafusa","year":"2024","journal-title":"Hum. Genome Var."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1681\/ASN.2016090938","article-title":"Polycystic Kidney Disease without an Apparent Family History","volume":"28","author":"Iliuta","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5414\/CN110704","article-title":"PKD1 Mosaicism Associated with Severe Renal, Hepatic, and Vascular Phenotype","volume":"98","author":"Dahan","year":"2022","journal-title":"Clin. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"464","DOI":"10.3389\/fgene.2020.00464","article-title":"Gene Panel Analysis in a Large Cohort of Patients With Autosomal Dominant Polycystic Kidney Disease Allows the Identification of 80 Potentially Causative Novel Variants and the Characterization of a Complex Genetic Architecture in a Subset of Families","volume":"11","author":"Mantovani","year":"2020","journal-title":"Front. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1681\/ASN.2011101032","article-title":"Identification of Gene Mutations in Autosomal Dominant Polycystic Kidney Disease through Targeted Resequencing","volume":"23","author":"Rossetti","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7354","DOI":"10.1039\/D0CS00647E","article-title":"Next-Generation DNA Damage Sequencing","volume":"49","author":"Mingard","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000468956","article-title":"Genetics and Autosomal Dominant Polycystic Kidney Disease Progression","volume":"190","author":"Corradi","year":"2017","journal-title":"Contrib. Nephrol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:57:05Z","timestamp":1760115425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["genes16010039"],"URL":"https:\/\/doi.org\/10.3390\/genes16010039","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]}}}