Joubert SyndromeJSCORSNCT00873678
Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
An observational study of Joubert Syndrome and Cerebello-oculo-renal Syndromes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Primary objective: assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) Secondary objective: assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JS/CORS caracterization of mutational spectrum of AHI1, NPHP1, CEP290 genes in… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Joubert Syndrome, Cerebello-oculo-renal Syndromes
- What is being tested?
- Whole blood sample
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2007to Jan 2010
- 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: Children or adult patients affected with JS/CORS
Who may be able to join
- Child or adult patients without age maximum
- Affected with JS/CORS défined by neurologic disease with at least one of the following symptoms :
- neonatal hypotonia or developmental delay (before age 3) or mental retardation (QD<70) (after age 3).
- Ataxia
- Oculomotor apraxia
- and on MRI :
- vermis hypoplasia/agenesia defined by insufficient development of cerebellar vermis.
- And molar tooth defined by thickened, elongated and mal-orientated superior cerebellar peduncles on axial sections.
Who cannot join
- Chromosomal anomalies identified by caryotype
- Absence of signature of informed consent.
- Absence of affiliation to social security
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes
Primary objective:
- assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS)
Secondary objective:
- assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JS/CORS
- caracterization of mutational spectrum of AHI1, NPHP1, CEP290 genes in JS/CORS.
- evaluation of genotype-phenotype correlation in JS/CORS.
Read the detailed description
Design: multicentric Aims of this study: to describe clinical and genetic basis of Joubert syndrome and cerebello-oculo-renal syndromes.Joubert syndrome (JS) is characterized by hypotonia, abnormal ocular movements and neonatal breathing dysregulation evolving into developmental delay, ataxia, oculomotor apraxia with variable mental retardation. The neuroradiological hallmark of JS is a complex midbrain-hindbrain malformation consisting of vermis hypoplasia/dysplasia, a deepened interpeduncular fossa, and thickened, elongated and mal-orientated superior cerebellar peduncles (Molar Tooth Sign, MTS). Other organs could be involved in JS (kidneys :nephronophthisis or cystic dysplastic kidneys; eyes : Leber Congenital Amaurosis, retinopathy, colobomas); liver : hepatic fibrosis; others: polydactyly, tongue hamartomas, situs inversus). Several associated central nervous system malformations were described : polymicrogyria, hydrocephalus, corpus callosum anomalies and encephalocele. This pleiotropic involvement identifies a large spectrum of cerebello-oculo-renal syndromes or JS Related Disorders (JSRD).
Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) are autosomal recessive conditions associated with a high risk of recurrence for further pregnancies (25%). In 2004 mutations in AHI1 gene (Abelson helper integration site gene) were identified in 7-11% JS but the disease is caracterized by a wide genetic heterogeneity. At least five others genes are involved in JS/CORS : NPHP1, which homozygous deletions are responsible for a small percentage of JS (2%) and more recently CEP290 gene which exact mutations prevalence remained to be evaluated.
Using molecular analysis of those three genes (sequencing of 29 coding exons of AHI1 and 54 exons of CEP290, searching for NPHP1 homozygous deletions by PCR analysis) we project to study respective prevalence of mutations of those three genes and described associated phenotypes in 65 JSCORS patients. This work will allowed to described genotype-phenotypes correlation in JSCORS and to progress in the characterization of the underlying pathogenetic mechanisms. It will be the first step before identification of novel disease genes.
- Conditions
- Joubert Syndrome, Cerebello-oculo-renal Syndromes
- Being tested
- Whole blood sample
- Keywords
- Molar tooth, AHI1 gene, CEP290 gene, ciliopathies
- Medical subject headings
- Agenesis of Cerebellar Vermis, Meckel Syndrome, Type 4, Ciliopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole blood sampleBiological
Whole blood sample (10 ml)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Children or adult patients affected with JS/CORS Receives: Biological: Whole blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS)
Measured: At the inclusion visit
Secondary outcomes (1)
Assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JS/CORS ; Caracterization of mutational spectrum of AHI1, NPHP1, CEP290 genes in JS/CORS ; Evaluation of genotype-phenotype correlation in JS/CORS.
Measured: At the inclusion visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2009 (estimated)
- Study startMar 2007
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Joubert SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Observational model
- Family based
- Time perspective
- Cross-sectional
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Investigators
- Lydie BURGLEN, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00873678
- Sponsor's protocol ID
- P051079
- Acronym
- JSCORS
- Status last verified
- Mar 2010
- First submitted
- 31 Mar 2009
- Last updated
- 3 Jun 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes
- ClinicalTrials.gov ID
- NCT00873678
- Acronym / sponsor ID
- JSCORS / P051079
- Conditions
- Joubert Syndrome, Cerebello-oculo-renal Syndromes
- Keywords
- Molar tooth, AHI1 gene, CEP290 gene, ciliopathies
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 1 Apr 2009 (estimated)
- 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.
Primary objective:
- assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS)
Secondary objective:
- assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JS/CORS
- caracterization of mutational spectrum of AHI1, NPHP1, CEP290 genes in JS/CORS.
- evaluation of genotype-phenotype correlation in JS/CORS.
Detailed description
Design: multicentric Aims of this study: to describe clinical and genetic basis of Joubert syndrome and cerebello-oculo-renal syndromes.Joubert syndrome (JS) is characterized by hypotonia, abnormal ocular movements and neonatal breathing dysregulation evolving into developmental delay, ataxia, oculomotor apraxia with variable mental retardation. The neuroradiological hallmark of JS is a complex midbrain-hindbrain malformation consisting of vermis hypoplasia/dysplasia, a deepened interpeduncular fossa, and thickened, elongated and mal-orientated superior cerebellar peduncles (Molar Tooth Sign, MTS). Other organs could be involved in JS (kidneys :nephronophthisis or cystic dysplastic kidneys; eyes : Leber Congenital Amaurosis, retinopathy, colobomas); liver : hepatic fibrosis; others: polydactyly, tongue hamartomas, situs inversus). Several associated central nervous system malformations were described : polymicrogyria, hydrocephalus, corpus callosum anomalies and encephalocele. This pleiotropic involvement identifies a large spectrum of cerebello-oculo-renal syndromes or JS Related Disorders (JSRD).
Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) are autosomal recessive conditions associated with a high risk of recurrence for further pregnancies (25%). In 2004 mutations in AHI1 gene (Abelson helper integration site gene) were identified in 7-11% JS but the disease is caracterized by a wide genetic heterogeneity. At least five others genes are involved in JS/CORS : NPHP1, which homozygous deletions are responsible for a small percentage of JS (2%) and more recently CEP290 gene which exact mutations prevalence remained to be evaluated.
Using molecular analysis of those three genes (sequencing of 29 coding exons of AHI1 and 54 exons of CEP290, searching for NPHP1 homozygous deletions by PCR analysis) we project to study respective prevalence of mutations of those three genes and described associated phenotypes in 65 JSCORS patients. This work will allowed to described genotype-phenotypes correlation in JSCORS and to progress in the characterization of the underlying pathogenetic mechanisms. It will be the first step before identification of novel disease genes.
Study design
- Observational model
- Family based
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Biological: Whole blood sampleChildren or adult patients affected with JS/CORS |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children or adult patients affected with JS/CORS
Key inclusion criteria (8 listed)
- Child or adult patients without age maximum
- Affected with JS/CORS défined by neurologic disease with at least one of the following symptoms :
- and on MRI :
Key exclusion criteria (3 listed)
- Chromosomal anomalies identified by caryotype
- Absence of signature of informed consent.
- Absence of affiliation to social security
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 |
|---|---|---|
| Whole blood sampleWhole blood sample (10 ml) | Biological | 1 |
Primary outcome
Assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS)
Time frame: At the inclusion visit
1 secondary outcome
Assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JS/CORS ; Caracterization of mutational spectrum of AHI1, NPHP1, CEP290 genes in JS/CORS ; Evaluation of genotype-phenotype correlation in JS/CORS.
Time frame: At the inclusion visit
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 3 Jun 2010.
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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.
Lydie BURGLEN, MD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Joubert Syndrome and Cerebello-oculo-renal Syndromes, run by Assistance Publique - Hôpitaux de Paris 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 8 inclusion and 3 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 3 Jun 2010. 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?
Assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) (time frame: At the inclusion visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jun 2010.