Trial record 1 of 3 for:    "Joubert syndrome"
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Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome (JSCORS)

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00873678
First received: March 31, 2009
Last updated: June 2, 2010
Last verified: March 2010
  Purpose

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.

Condition Intervention
Joubert Syndrome
Cerebello-oculo-renal Syndromes
Biological: Whole blood sample

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Cross-Sectional
Official Title: Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) [ Time Frame: At the inclusion visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Whole blood sample (10 ml)


Enrollment: 80
Study Start Date: March 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Children or adult patients affected with JS/CORS
Biological: Whole blood sample
Whole blood sample (10 ml)
Other Name: Whole blood sample

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children or adult patients affected with JS/CORS

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Chromosomal anomalies identified by caryotype
  • Absence of signature of informed consent.
  • Absence of affiliation to social security
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00873678

Locations
France
Hopital Trousseau
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Lydie BURGLEN, MD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Amel Ouslimani, Department Clinical Research of Developpement
ClinicalTrials.gov Identifier: NCT00873678     History of Changes
Other Study ID Numbers: P051079
Study First Received: March 31, 2009
Last Updated: June 2, 2010
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Molar tooth
AHI1 gene
CEP290 gene
ciliopathies

Additional relevant MeSH terms:
Cerebellar Diseases
Eye Abnormalities
Kidney Diseases, Cystic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Eye Diseases
Congenital Abnormalities
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on April 16, 2014