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Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome (JSCORS)

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ClinicalTrials.gov Identifier: NCT00873678
Recruitment Status : Completed
First Posted : April 1, 2009
Last Update Posted : June 3, 2010
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date March 31, 2009
First Posted Date April 1, 2009
Last Update Posted Date June 3, 2010
Study Start Date March 2007
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 31, 2009)
Assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) [ Time Frame: At the inclusion visit ]
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT00873678 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: March 31, 2009)
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 ]
Original Secondary Outcome Measures Same as current
Current Other Outcome Measures Not Provided
Original Other Outcome Measures Not Provided
 
Descriptive Information
Brief Title Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
Official Title Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes
Brief 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 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 Type Observational
Study Design Observational Model: Family-Based
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Whole blood sample (10 ml)
Sampling Method Non-Probability Sample
Study Population Children or adult patients affected with JS/CORS
Condition
  • Joubert Syndrome
  • Cerebello-oculo-renal Syndromes
Intervention Biological: Whole blood sample
Whole blood sample (10 ml)
Study Groups/Cohorts 1
Children or adult patients affected with JS/CORS
Intervention: Biological: Whole blood sample
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: June 2, 2010)
80
Original Estimated Enrollment
 (submitted: March 31, 2009)
65
Actual Study Completion Date January 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT00873678
Other Study ID Numbers P051079
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Amel Ouslimani, Department Clinical Research of Developpement
Study Sponsor Assistance Publique - Hôpitaux de Paris
Collaborators Not Provided
Investigators
Principal Investigator: Lydie BURGLEN, MD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date March 2010