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Sponsored by: |
Assistance Publique - Hôpitaux de Paris |
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Information provided by: | Assistance Publique - Hôpitaux de Paris |
ClinicalTrials.gov Identifier: | NCT00873678 |
Primary objective:
Secondary objective:
Condition | Intervention |
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Joubert Syndrome Cerebello-Oculo-Renal Syndromes |
Biological: Whole blood sample |
Study Type: | Observational |
Study Design: | Family-Based, 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 |
Whole blood sample (10 ml)
Estimated Enrollment: | 65 |
Study Start Date: | March 2007 |
Estimated Study Completion Date: | September 2009 |
Estimated Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
Groups/Cohorts | Assigned Interventions |
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1
Children or adult patients affected with JS/CORS
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Biological: Whole blood sample
Whole blood sample (10 ml)
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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.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Children or adult patients affected with JS/CORS
Inclusion Criteria:
Affected with JS/CORS défined by neurologic disease with at least one of the following symptoms :
and on MRI :
Exclusion Criteria:
Contact: Lydie Burglen, MD | lydie.burglen@trs.aphp.fr |
France | |
Hopital Trousseau | Recruiting |
Paris, France, 75012 | |
Contact: Lydie Burglen, MD lydie.burglen@trs.aphp.fr | |
Principal Investigator: Lydie Burglen, MD |
Principal Investigator: | Lydie BURGLEN, MD | Assistance Publique - Hôpitaux de Paris |
Responsible Party: | Amel Ouslimani ( Direction Interrégionale de la Recherche Clinique ) |
Study ID Numbers: | P051079, CRC 05145 |
Study First Received: | March 31, 2009 |
Last Updated: | March 31, 2009 |
ClinicalTrials.gov Identifier: | NCT00873678 History of Changes |
Health Authority: | France: Ministry of Health |
Molar tooth AHI1 gene CEP290 gene ciliopathies |
Apnea Eye Diseases Respiration Disorders Central Nervous System Diseases Dyskinesias Ocular Motility Disorders Signs and Symptoms |
Respiratory Tract Diseases Joubert Syndrome 1 Muscle Hypotonia Ataxia Signs and Symptoms, Respiratory Neurologic Manifestations Motor Neuro-ophthalmic Disorders |
Neuromuscular Manifestations Disease Apnea Eye Diseases Nervous System Diseases Respiration Disorders Central Nervous System Diseases Dyskinesias Ocular Motility Disorders |
Signs and Symptoms Pathologic Processes Respiratory Tract Diseases Syndrome Muscle Hypotonia Ataxia Signs and Symptoms, Respiratory Neurologic Manifestations Cranial Nerve Diseases |