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Case Reports
. 2024 Dec 30;16(1):39.
doi: 10.3390/genes16010039.

Typical Clinical Presentation of an Autosomal Dominant Polycystic Kidney Disease Patient with an Atypical Genetic Pattern

Nenzi Marzano  1 , Carlotta Caprara  1   2   3 , Thiago Reis  1   4   5   6 , Diego Pomarè Montin  1   7 , Sofia Maria Pretto  1 , Matteo Rigato  1   2 , Anna Giuliani  2 , Fiorella Gastaldon  2 , Barbara Mancini  3 , Claudio Ronco  1 , Monica Zanella  1   2 , Daniela Zuccarello  3 , Valentina Corradi  1   2
Affiliations
Case Reports

Typical Clinical Presentation of an Autosomal Dominant Polycystic Kidney Disease Patient with an Atypical Genetic Pattern

Nenzi Marzano et al. Genes (Basel). .

Abstract

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 2-34 of PKD1) present in the heterozygosis with a percentage of cells close to the resolution limits of the technique used (<25-30%). 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's 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.

Keywords: chronic kidney disease; mosaicism; multiple ligation-dependent probe amplification; next-generation sequencing; polycystic kidney disease.

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Conflict of interest statement

T.R. has received funding for lectures and has been a consultant or advisory board member for Alexion, AstraZeneca, B. Braun, Baxter, bioMérieux, Boehringer Ingelheim, Contatti (CytoSorbents), Eurofarma, George Clinical, Jafron, Lifepharma, Medcorp, Nipro, and Nova Biomedical. C.R. has been on advisory boards or speaker’s bureau for AstraZeneca, Aferetica, Asahi, B. Braun, Baxter, bioMérieux, CytoSorbents, GE, Medica, Medtronic, and Jafron. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Analysis with multiplex ligation probe amplification (MLPA) of PKD1 gene (light blue and orange background) (NM_001009944.3, except exons 1, 2, 4, 8, 17, 24, 28, 32, 34, 45) and of PKD2 gene (blue background) (NM_000297.4, ecept exon 13). The molecular investigation was performed on genomic DNA using Kit Salsa MLPA ProbeMix P352-D1 PKD1-PKD2 and ProbeMix P351-C1 PKD1 ©MRC Holland. The result shows a deletion of the 3–33 exons of the PKD1 gene in mosaic. The arrangement of probes based on chromosomal position reveals a heterozygous deletion (red line): probe ratio <0.5 (red dots), probe ratio 1 < x < 0.5 (purple dots). The first deleted probe was number 141 on the PKD1 gene (hg18 loc.16-002.109164) (b), while the last was number 416 on the PKD1 gene (hg18 loc.16-002.087302) (a). Black dots represent boundedprobes; exons are represented by light blue boxes (green boxes are reference exons). Results are displayed by the Coffalyser.Net software (https://www.mrcholland.com/technology/software/coffalyser-net, accessed on 22 December 2024).
Figure 2
Figure 2
Analysis with multiplex ligation probe amplification (MLPA) of PKD1 gene (light blue and orange background) (NM_001009944.3, except exons 4, 8, 17, 28, 32) and of PKD2 gene (blue background) (NM_000297.4). The molecular investigation was performed on genomic DNA using the revised Kit Salsa MLPA ProbeMix P352-E1 PKD1PKD2 (a) and ProbeMix P351-D1 PKD1 ©MRC Holland (b). The result shows a deletion of the 2–34 exons of the PKD1 gene in mosaic: NC_000016.10: g. (2136179_2119520) (2097184_2094247) del, chr16:2094247: 2136179: del. (Chr NCBI36/hg18). The arrangement of probes based on chromosomal position reveals a heterozygous deletion (red line): probe ratio <0.5 (red dots), probe ratio 1 < x < 0.5 (purple dots). The first deleted probe was the 240 on the PKD1 gene (hg18 loc.16-002.109510) (a), while the last was the 208 on the PKD1 gene (hg18 loc.16-002.087160) (a). Black dots represent bounded probes; exons are represented by light blue boxes (green boxes are reference exons). Results are displayed by the Coffalyser.Net software.
Figure 2
Figure 2
Analysis with multiplex ligation probe amplification (MLPA) of PKD1 gene (light blue and orange background) (NM_001009944.3, except exons 4, 8, 17, 28, 32) and of PKD2 gene (blue background) (NM_000297.4). The molecular investigation was performed on genomic DNA using the revised Kit Salsa MLPA ProbeMix P352-E1 PKD1PKD2 (a) and ProbeMix P351-D1 PKD1 ©MRC Holland (b). The result shows a deletion of the 2–34 exons of the PKD1 gene in mosaic: NC_000016.10: g. (2136179_2119520) (2097184_2094247) del, chr16:2094247: 2136179: del. (Chr NCBI36/hg18). The arrangement of probes based on chromosomal position reveals a heterozygous deletion (red line): probe ratio <0.5 (red dots), probe ratio 1 < x < 0.5 (purple dots). The first deleted probe was the 240 on the PKD1 gene (hg18 loc.16-002.109510) (a), while the last was the 208 on the PKD1 gene (hg18 loc.16-002.087160) (a). Black dots represent bounded probes; exons are represented by light blue boxes (green boxes are reference exons). Results are displayed by the Coffalyser.Net software.
Figure 3
Figure 3
Genetic analysis workflow conducted in sequence.
See this image and copyright information in PMC

References

    1. Hildebrandt F., Benzing T., Katsanis N. Ciliopathies. N. Engl. J. Med. 2011;364:1533–1543. doi: 10.1056/NEJMra1010172. - DOI - PMC - PubMed
    1. Burgmaier K., Gimpel C., Schaefer F., Liebau M. Autosomal Recessive Polycystic Kidney Disease—PKHD1. University of Washington; Seattle, WA, USA: 1993.
    1. Corradi V., Gastaldon F., Virzì G.M., Clementi M., Nalesso F., Cruz D.N., De Cal M., Torregrossa R., Ronco C. 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? G. Ital. Nefrol. 2010;27:655–663. - PubMed
    1. Solazzo A., Testa F., Giovanella S., Busutti M., Furci L., Carrera P., Ferrari M., Ligabue G., Mori G., Leonelli M., et al. 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. PLoS ONE. 2018;13:e0190430. doi: 10.1371/journal.pone.0190430. - DOI - PMC - PubMed
    1. Corradi V., Gastaldon F., Virzì G.M., De Cal M., Soni S., Chionh C., Cruz D.N., Clementi M., Ronco C. Clinical Pattern of Adult Polycystic Kidney Disease in a Northeastern Region of Italy. Clin. Nephrol. 2009;72:259–267. doi: 10.5414/CNP72259. - DOI - PubMed

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