Developmental DisordersRRMUTNCT04564235
Risk of Recurrence of de Novo Mutations: Research and Quantification of Paternal Germinal Mosaicism by the Combined Use of Genomic Tools
A study testing genome-wide analyses and Search for de novo mutations in paternal sperm samples in people with Developmental Disorders, run by University Hospital, Rouen at 1 site in France.
Trial summary
1. Inclusion of 5 families Inclusions will be made by the clinical genetics department of the Rouen University Hospital (monocentric study) and will correspond to trios of parents + child with unexplained developmental abnormalities. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Developmental Disorders
- What is being tested?
- genome-wide analyses and Search for de novo mutations in paternal sperm samples
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- 24 Feb 2021to 12 Dec 2022
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Trio consisting of a child with a developmental disorder and both unaffected parents
- Absence of etiology after clinical expertise and genetic testing
- Indication of a genome-wide sequencing analysis
- Child from spontaneous pregnancy without ovulation stimulation treatment
- Availability of DNA blood samples
- Affiliation to a social insurance
- Patient or patient's legal representative who has read and understood the information letter and has signed the consent form
Who cannot join
- Lack of indication for a genome-wide analysis in the proband
- Etiology of the developmental disorder already identified
- Proband born after In-Vitro Fertilization
- Impossibility of non-invasive sperm collection from the father
Trial locations and contacts
1 site in 1 country.
About this study
- Inclusion of 5 families Inclusions will be made by the clinical genetics department of the Rouen University Hospital (monocentric study) and will correspond to trios of parents + child with unexplained developmental abnormalities. The inclusion of patients will be integrated in routine care and will have as immediate benefit for the included families the extensive analysis of the proband and their parents' genomes by short and long read sequencing techniques, which represent the most comprehensive diagnostic tests for developmental diseases, and which are not currently routinely available. Inclusion in clinical genetics by clinicians accustomed to prescribing genome-wide analyses will allow clear and complete information to families. Collection of consents. The trio's DNA will already be available at the molecular genetics laboratory, and a new blood sample may be proposed if necessary. Collection of sperm from the father.
- Identification of a large set of de novo mutations. Extraction of blood DNA and sending for sequencing of the complete genome to the National Centre for Research in Human Genomics (CNRGH, Evry), in the framework of a collaboration already initiated. Analysis of the sequencing data thanks to the already existing expertise in Rouen. Identification of about 40-120 de novo mutations per trio. At this stage: interpretation of the variations identified with the secondary objective of identifying the cause of the disease in children. Long read genomes will allow to phase the de novo variants to the paternal or to the maternal haplotype.
- Search for de novo mutations in paternal sperm samples. Extraction of spermatic DNA. Design of a sequencing panel targeting the genetic variations identified in the different trios. Preparation of the libraries, targeted high throughput sequencing at great depth thanks to the techniques and equipment already operational. Specific search for the de novo variations identified in the probands (in 2.), with for each evaluation of (i) the presence of the variation in the sperm sample, (ii) the quantity of mosaicism, reflecting the proportion of carrier spermatozoa and therefore the risk of recurrence, (iii) the presence of my variation in the blood sample of both parents in deep sequencing.
- Conditions
- Developmental Disorders
- Being tested
- genome-wide analyses, Search for de novo mutations in paternal sperm samples
- Medical subject headings
- Developmental Disabilities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
genome-wide analysesGenetic
genome-wide analyses will be done in patients and parents (father, mother)
Search for de novo mutations in paternal sperm samplesGenetic
Sperm analysis will be done in paternal samples
| Study group | Role | What they receive |
|---|---|---|
| Indication for a genome-wide analysis in the proband | Experimental | Not described Receives: Genetic: genome-wide analyses; Genetic: Search for de novo mutations in paternal sperm samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of the patient's de novo mutations detectable in the father's sperm
Measured: Day 1
Secondary outcomes (1)
Number of patients for whom molecular diagnosis has been obtained (cause of developmental disability identified) ≥1
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start24 Feb 2021
- Primary completion12 Dec 2022
- Study completion12 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Developmental DisordersStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François LECOQUIERRE, MD, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04564235
- Sponsor's protocol ID
- 2019/0401/HP
- Acronym
- RRMUT
- Status last verified
- Feb 2026
- First submitted
- 21 Sep 2020
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lecoquierre F, Drouot N, Coutant S, Quenez O, Fourneaux S, Jumeau F, Rives N, Charbonnier F, Derambure C, Boland A, Olaso R, Meyer V, Deleuze JF, Goldenberg A, Guerrot AM, Charbonnier C, Nicolas G. Parental germline mosaicism in genome-wide phased de novo variants: Recurrence risk assessment and implications for precision genetic counselling. PLoS Genet. 2025 Mar 31;21(3):e1011651. doi: 10.1371/journal.pgen.1011651. eCollection 2025 Mar.
PubMed 40163539Lecoquierre F, Quenez O, Fourneaux S, Coutant S, Vezain M, Rolain M, Drouot N, Boland A, Olaso R, Meyer V, Deleuze JF, Dabbagh D, Gilles I, Gayet C, Saugier-Veber P, Goldenberg A, Guerrot AM, Nicolas G. High diagnostic potential of short and long read genome sequencing with transcriptome analysis in exome-negative developmental disorders. Hum Genet. 2023 Jun;142(6):773-783. doi: 10.1007/s00439-023-02553-1. Epub 2023 Apr 19.
PubMed 37076692
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Recurrence of de Novo Mutations: Research and Quantification of Paternal Germinal Mosaicism by the Combined Use of Genomic Tools
- ClinicalTrials.gov ID
- NCT04564235
- Acronym / sponsor ID
- RRMUT / 2019/0401/HP
- Conditions
- Developmental Disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 24 Feb 2021 (actual)
- Primary completion
- 12 Dec 2022 (actual)
- Study completion
- 12 Dec 2022 (actual)
- First posted
- 25 Sep 2020 (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.
- Inclusion of 5 families Inclusions will be made by the clinical genetics department of the Rouen University Hospital (monocentric study) and will correspond to trios of parents + child with unexplained developmental abnormalities. The inclusion of patients will be integrated in routine care and will have as immediate benefit for the included families the extensive analysis of the proband and their parents' genomes by short and long read sequencing techniques, which represent the most comprehensive diagnostic tests for developmental diseases, and which are not currently routinely available. Inclusion in clinical genetics by clinicians accustomed to prescribing genome-wide analyses will allow clear and complete information to families. Collection of consents. The trio's DNA will already be available at the molecular genetics laboratory, and a new blood sample may be proposed if necessary. Collection of sperm from the father.
- Identification of a large set of de novo mutations. Extraction of blood DNA and sending for sequencing of the complete genome to the National Centre for Research in Human Genomics (CNRGH, Evry), in the framework of a collaboration already initiated. Analysis of the sequencing data thanks to the already existing expertise in Rouen. Identification of about 40-120 de novo mutations per trio. At this stage: interpretation of the variations identified with the secondary objective of identifying the cause of the disease in children. Long read genomes will allow to phase the de novo variants to the paternal or to the maternal haplotype.
- Search for de novo mutations in paternal sperm samples. Extraction of spermatic DNA. Design of a sequencing panel targeting the genetic variations identified in the different trios. Preparation of the libraries, targeted high throughput sequencing at great depth thanks to the techniques and equipment already operational. Specific search for the de novo variations identified in the probands (in 2.), with for each evaluation of (i) the presence of the variation in the sperm sample, (ii) the quantity of mosaicism, reflecting the proportion of carrier spermatozoa and therefore the risk of recurrence, (iii) the presence of my variation in the blood sample of both parents in deep sequencing.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Indication for a genome-wide analysis in the proband | Experimental | Genetic: genome-wide analyses, Genetic: Search for de novo mutations in paternal sperm samples |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Trio consisting of a child with a developmental disorder and both unaffected parents
- Absence of etiology after clinical expertise and genetic testing
- Indication of a genome-wide sequencing analysis
- Child from spontaneous pregnancy without ovulation stimulation treatment
- Availability of DNA blood samples
Key exclusion criteria (4 listed)
- Lack of indication for a genome-wide analysis in the proband
- Etiology of the developmental disorder already identified
- Proband born after In-Vitro Fertilization
- Impossibility of non-invasive sperm collection from the father
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| genome-wide analysesgenome-wide analyses will be done in patients and parents (father, mother) | Genetic | Indication for a genome-wide analysis in the proband |
| Search for de novo mutations in paternal sperm samplesSperm analysis will be done in paternal samples | Genetic | Indication for a genome-wide analysis in the proband |
Primary outcome
Proportion of the patient's de novo mutations detectable in the father's sperm
Time frame: Day 1
1 secondary outcome
Number of patients for whom molecular diagnosis has been obtained (cause of developmental disability identified) ≥1
Time frame: Day 1
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 20 Apr 2026.
- Results publication: PubMed 40163539Lecoquierre F, Drouot N, Coutant S, Quenez O, Fourneaux S, Jumeau F, Rives N, Charbonnier F, Derambure C, Boland A, Olaso R, Meyer V, Deleuze JF, Goldenberg A, Guerrot AM, Charbonnier C, Nicolas G. Parental germline mosaicism in genome-wide phased de novo variants: Recurrence risk assessment and implications for precision genetic counselling. PLoS Genet. 2025 Mar 31;21(3):e1011651. doi: 10.1371/journal.pgen.1011651. eCollection 2025 Mar.
- Results publication: PubMed 37076692Lecoquierre F, Quenez O, Fourneaux S, Coutant S, Vezain M, Rolain M, Drouot N, Boland A, Olaso R, Meyer V, Deleuze JF, Dabbagh D, Gilles I, Gayet C, Saugier-Veber P, Goldenberg A, Guerrot AM, Nicolas G. High diagnostic potential of short and long read genome sequencing with transcriptome analysis in exome-negative developmental disorders. Hum Genet. 2023 Jun;142(6):773-783. doi: 10.1007/s00439-023-02553-1. Epub 2023 Apr 19.
- Individual participant dataSharing planned: No
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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.
François LECOQUIERRE, MD principal investigator
University Hospital, Rouen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing genome-wide analyses and Search for de novo mutations in paternal sperm samples in people with Developmental Disorders, run by University Hospital, Rouen at 1 site in France.
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 7 inclusion and 4 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 20 Apr 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 France. 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?
Proportion of the patient's de novo mutations detectable in the father's sperm (time frame: Day 1). 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 NCT04564235, which also lists 2 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 20 Apr 2026.