Autosomal Dominant Polycystic Kidney Disease (ADPKD)POPULARNCT06594367
A Possible Founding PKD2 Mutation Associated With Variable Phenotypes of ADPKD in Bergamo Province
An observational study of Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
This is an observational study aimed at assessing if a new and specific heterozygous deletion detected at PKD2 gene is associated to a "founder effect" in 10 Autosomal dominant polycystic kidney disease (ADPKD) patients, and at investigating the genotype-phenotype correlation in the families sharing the same PKD2… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 22 Jan 2025to 31 Oct 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Italian cohort of ADPKD patients who were referred to the Clinical Research Centre for Rare Diseases Aldo e Cele Daccò for genetic analysis through the Italian National Health Service.
Who may be able to join
- Patients with ADPKD
Who cannot join
- Healthy patients
Trial locations and contacts
1 site in 1 country.
Italy1 site
Clinical Research Centre for Rare Diseases Aldo e Cele Daccò
Ranica, BG, 24020
About this study
This is an observational study aimed at assessing if a new and specific heterozygous deletion detected at PKD2 gene is associated to a "founder effect" in 10 Autosomal dominant polycystic kidney disease (ADPKD) patients, and at investigating the genotype-phenotype correlation in the families sharing the same PKD2 breakpoint site.
Read the detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are located in two genes: PKD1 and PKD2. They account for 78% and 13% of ADPKD cases, respectively, while in approximately 6-9% of clinically diagnosed patients other genes have been shown to contribute to the disease.
Most ADPKD mutations are private and so far no hot-spot mutations have been reported in PKD1 and PKD2. On average, renal survival of patients with PKD2 mutations is 20 years longer than in patients with PKD1 mutations. However, there is a high degree of clinical variability among patients as well as within families, with different rates of progression towards end-stage renal disease (ESRD), partially driven by genetic factors.
Few reports are available about possible founding mutations in ADPKD. We have recently reported the results of genetic analysis for PKD1 and PKD2 by Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) in a large Italian cohort of ADPKD patients who were referred to our center for genetic analysis through the Italian National Health Service.
MLPA is a method for detecting copy number variation (CNV) of a specific DNA segment within the genome, suggestive of duplications, deletions or other structural variants that may affect long DNA stretches. The exact characterization of the extent of the structural variant identified by MLPA, however, requires subsequent analyses.
In 4 families (6 patients) who were negative at Sanger sequencing, MLPA analysis of PKD2 revealed a novel heterozygous copy number variation (CNV) indicative of a deletion of at least 11,000 base pairs (bp) and spanning exons 1-2. These families are formally not related, but they live in the same geographical area including three small villages in Bergamo province (Torre de Roveri, Albano S. Alessandro, Scanzorosciate), suggesting a potential founder effect. More recently, we detected the same PKD2 CNV in 3 additional families (4 patients) from the same geographical area, further strengthening this hypothesis. Most affected subjects in these families have mild disease, as expected for PKD2 mutations, but one patient experienced early ESRD and another one presents congenital anomalies of the kidney and the urinary tract (CAKUT) in addition to the typical ADPKD phenotype, indicating a different expressivity of the disease or the possible presence of other genetic factors affecting the clinical phenotype.
Further in depth analyses were needed to investigate the deletion of at least 11,000 base pairs (bp) and spanning exons 1-2 to find the breakpoint site in the 10 patients for diagnostic purpose. We found the same breakpoint sites across all the patients pointing to a common origin, and similar disease expressivity.
- Keywords
- PKD2 mutation, founder effect, Bergamo province, variable phenotype
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients | 10 patients from di 7 families living in 3 villages of the Bergamo province i.e., Torre de Roveri, Albano S. Alessandro and Scanzorosciate who during genetic tests for ADPKD have revealed the presence of a new heterozygous deletion in the PKD2 gene will be included in this study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of a deletion
Evidence of an heterozygous copy number variation (CNV) indicative of a deletion of at least 11,000 base pairs (bp) and spanning exons 1-2 (DNA amplification by long-range PCR).
Measured: At day 1
Genetic counseling
All the patients sharing the same PKD2 deletion will be interviewed about their personal and familial anamnesis. Starting from the pedigree and the detailed family medical history, the genotype-phenotype correlation will be defined and other potentially affected family members, if any, will be identified.
Measured: At day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start22 Jan 2025
- Primary completion17 Oct 2025
- Study completion31 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06594367
- Sponsor's protocol ID
- POPULAR
- Acronym
- POPULAR
- Status last verified
- Mar 2026
- First submitted
- 2 Sep 2024
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Orisio S, Noris M, Rigoldi M, Bresin E, Perico N, Trillini M, Donadelli R, Perna A, Benigni A, Remuzzi G. Mutation Analysis of PKD1 and PKD2 Genes in a Large Italian Cohort Reveals Novel Pathogenic Variants Including a Novel Complex Rearrangement. Nephron. 2024;148(5):273-291. doi: 10.1159/000530657. Epub 2023 May 25.
PubMed 37231942Willey CJ, Blais JD, Hall AK, Krasa HB, Makin AJ, Czerwiec FS. Prevalence of autosomal dominant polycystic kidney disease in the European Union. Nephrol Dial Transplant. 2017 Aug 1;32(8):1356-1363. doi: 10.1093/ndt/gfw240.
PubMed 27325254Cornec-Le Gall E, Audrezet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Ferec C, Le Meur Y. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol. 2013 May;24(6):1006-13. doi: 10.1681/ASN.2012070650. Epub 2013 Feb 21.
PubMed 23431072
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Possible Founding PKD2 Mutation Associated With Variable Phenotypes of ADPKD in Bergamo Province
- ClinicalTrials.gov ID
- NCT06594367
- Acronym / sponsor ID
- POPULAR / POPULAR
- Keywords
- PKD2 mutation, founder effect, Bergamo province, variable phenotype
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 22 Jan 2025 (actual)
- Primary completion
- 17 Oct 2025 (actual)
- Study completion
- 31 Oct 2025 (actual)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an observational study aimed at assessing if a new and specific heterozygous deletion detected at PKD2 gene is associated to a "founder effect" in 10 Autosomal dominant polycystic kidney disease (ADPKD) patients, and at investigating the genotype-phenotype correlation in the families sharing the same PKD2 breakpoint site.
Detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are located in two genes: PKD1 and PKD2. They account for 78% and 13% of ADPKD cases, respectively, while in approximately 6-9% of clinically diagnosed patients other genes have been shown to contribute to the disease.
Most ADPKD mutations are private and so far no hot-spot mutations have been reported in PKD1 and PKD2. On average, renal survival of patients with PKD2 mutations is 20 years longer than in patients with PKD1 mutations. However, there is a high degree of clinical variability among patients as well as within families, with different rates of progression towards end-stage renal disease (ESRD), partially driven by genetic factors.
Few reports are available about possible founding mutations in ADPKD. We have recently reported the results of genetic analysis for PKD1 and PKD2 by Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) in a large Italian cohort of ADPKD patients who were referred to our center for genetic analysis through the Italian National Health Service.
MLPA is a method for detecting copy number variation (CNV) of a specific DNA segment within the genome, suggestive of duplications, deletions or other structural variants that may affect long DNA stretches. The exact characterization of the extent of the structural variant identified by MLPA, however, requires subsequent analyses.
In 4 families (6 patients) who were negative at Sanger sequencing, MLPA analysis of PKD2 revealed a novel heterozygous copy number variation (CNV) indicative of a deletion of at least 11,000 base pairs (bp) and spanning exons 1-2. These families are formally not related, but they live in the same geographical area including three small villages in Bergamo province (Torre de Roveri, Albano S. Alessandro, Scanzorosciate), suggesting a potential founder effect. More recently, we detected the same PKD2 CNV in 3 additional families (4 patients) from the same geographical area, further strengthening this hypothesis. Most affected subjects in these families have mild disease, as expected for PKD2 mutations, but one patient experienced early ESRD and another one presents congenital anomalies of the kidney and the urinary tract (CAKUT) in addition to the typical ADPKD phenotype, indicating a different expressivity of the disease or the possible presence of other genetic factors affecting the clinical phenotype.
Further in depth analyses were needed to investigate the deletion of at least 11,000 base pairs (bp) and spanning exons 1-2 to find the breakpoint site in the 10 patients for diagnostic purpose. We found the same breakpoint sites across all the patients pointing to a common origin, and similar disease expressivity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | – | –10 patients from di 7 families living in 3 villages of the Bergamo province i.e., Torre de Roveri, Albano S. Alessandro and Scanzorosciate who during genetic tests for ADPKD have revealed the presence of a new heterozygous deletion in the PKD2 gene will be included in this study. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Italian cohort of ADPKD patients who were referred to the Clinical Research Centre for Rare Diseases Aldo e Cele Daccò for genetic analysis through the Italian National Health Service.
Key inclusion criteria (1 listed)
- Patients with ADPKD
Key exclusion criteria (1 listed)
- Healthy patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Evidence of a deletion
Time frame: At day 1
Evidence of an heterozygous copy number variation (CNV) indicative of a deletion of at least 11,000 base pairs (bp) and spanning exons 1-2 (DNA amplification by long-range PCR).
Genetic counseling
Time frame: At day 1
All the patients sharing the same PKD2 deletion will be interviewed about their personal and familial anamnesis. Starting from the pedigree and the detailed family medical history, the genotype-phenotype correlation will be defined and other potentially affected family members, if any, will be identified.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Background: PubMed 37231942Orisio S, Noris M, Rigoldi M, Bresin E, Perico N, Trillini M, Donadelli R, Perna A, Benigni A, Remuzzi G. Mutation Analysis of PKD1 and PKD2 Genes in a Large Italian Cohort Reveals Novel Pathogenic Variants Including a Novel Complex Rearrangement. Nephron. 2024;148(5):273-291. doi: 10.1159/000530657. Epub 2023 May 25.
- Background: PubMed 27325254Willey CJ, Blais JD, Hall AK, Krasa HB, Makin AJ, Czerwiec FS. Prevalence of autosomal dominant polycystic kidney disease in the European Union. Nephrol Dial Transplant. 2017 Aug 1;32(8):1356-1363. doi: 10.1093/ndt/gfw240.
- Background: PubMed 23431072Cornec-Le Gall E, Audrezet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Ferec C, Le Meur Y. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol. 2013 May;24(6):1006-13. doi: 10.1681/ASN.2012070650. Epub 2013 Feb 21.
- Individual participant dataSharing planned: No
Related trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Active, not recruitingObservational study
Polycystic Kidney Disease 1 (PKD1) Gene Variant Groups in Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Not yet recruitingEarly Phase 1
GBP-213 in Patients With Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney
RecruitingPhase 1
Safety, Tolerability and Pharmacokinetics of AZD1613 in Adults With Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Not yet recruitingPhase 1
Absorption, Distribution, Metabolism, and Excretion of 14C-VX-407 After a Single Oral Dose
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
RecruitingPhase 2
ANCHOR Study: A Study to Assess the Safety and Efficacy of ABBV-CLS-628 in Adult Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Autosomal Dominant Polycystic Kidney Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evidence of a deletion (time frame: At day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06594367, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.