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Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias (ATAXIC)
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Purpose
Congenital ataxias (CA) are rare, non progressive diseases, characterized by psychomotor retardation, hypotonia followed by ataxia. The presence of the "molar tooth" on MRI allowed to define Joubert syndrome, a peculiar form of CA. Apart from this group, CA are mostly associated with cerebellar atrophy or hypoplasia without molar tooth on MRI. CA are a clinically as well as genetically heterogeneous group of diseases. Early-onset ataxias are progressive but may be difficult to distinguish from CA in the first years of the disease. To date, few genes responsible for CA have been identified: ABC7 (X-linked CA associated with sideroblastic anemia), SLC9A6 (X-linked CA associated with severe mental retardation, autism and epilepsy), GPR56 (CA associated with polymicrogyria), ATCAY (pure CA in Cayman isolate); the involvement of the ATCAY and ABC7 genes has never been assessed in a large cohort of CA patients.
Primary objective:
To assess the frequency of mutations of the ATCAY and ABC7 genes in patients affected with non Joubert congenital or early-onset ataxia.
Secondary objective:
To identify new loci and/or genes responsible for CA To further describe the clinical phenotype of the CA and to assess the frequency of the various clinical types (pure CA/CA associated with spasticity/ syndromic CA, congenital/early-onset CA, sporadic/familial CA).
To describe the clinical phenotype of CA related to mutations in one of analysed genes.
| Condition | Intervention |
|---|---|
| Congenital Cerebellar Ataxias Early-onset Cerebellar Ataxias | Genetic: blood sample |
| Study Type: | Observational |
| Study Design: | Observational Model: Family-Based |
| Official Title: | Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias |
- Percentage of the patients with a mutation in one of the analysed genes. [ Time Frame: 1 day ]
- Percentage of patients with severe/moderate/mild/absent intellectual deficiency [ Time Frame: 1 day ]
- Percentage of patients with/without epilepsy/spasticity/extraneurological features and nature and frequency of MRI anomalies [ Time Frame: 1 day ]
Biospecimen Retention: Samples With DNA
| Enrollment: | 165 |
| Study Start Date: | January 2012 |
| Study Completion Date: | October 2014 |
| Primary Completion Date: | October 2014 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
| patients ataxic |
Genetic: blood sample
Blood sample will be analysed in order to check presence or not of mutation in ABC7, SLC9A6, GPR56, ATCAY.
|
Detailed Description:
All patients will be examined by a geneticist or a neuropediatric. All clinical data will be collected.
Strategy of the molecular study :
- for all multiplex and consanguineous families a linkage analysis (loci ATCAY and ABC7 and others AC known genes) will be performed.
- For all sporadic patients as well as linked multiplex and consanguineous families : sequencing of all coding exons of the gene ATCAY and others AC known genes.
- For all sporadic male patients and linked families : sequencing of all coding exons of the gene ABC7.
- For all patients with suggestive features : sequencing of all coding exons of the gene GPR56, VLDLR, NHE6 or other candidate gene.
- In consanguineous families : linkage analysis using SNP-array and analysis of candidate genes present in the regions of extended homozygosity
- linkage analysis in dominant families and analysis of candidate genes in the linked regions.
- If a new AC locus is identified (using linkage or CGH array), this gene will be sequenced in all patients.
Eligibility| Ages Eligible for Study: | Child, Adult, Senior |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- Patient, child or adult, affected with a congenital or early-onset ataxia defined by:
- Neurological symptoms observed before age of 2 years.
- Non progressive cerebellar ataxia observed at the time of examination. Karyotype done or in progress
Exclusion Criteria:
- Metabolic disease
- Specific MRI malformations suggesting a peculiar entity : molar tooth (joubert syndrome), superior vermis dysplasia with cleft (Oligophrenin)
- Muscle weakness and elevated creatine phosphokinase (CPK)
- Clearly progressive ataxia.
- Absence of signature of the informed consent.
- Absence of affiliation to social security
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01488461
| France | |
| Hôpital Trousseau, Service de Génétique | |
| Paris, France, 75012 | |
| Principal Investigator: | Lydie Burglen, PhD | Assistance Publique |
More Information
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT01488461 History of Changes |
| Other Study ID Numbers: |
NI 08034 AOM 09178 ( Other Identifier: Assistance Publique ) |
| Study First Received: | December 6, 2011 |
| Last Updated: | June 12, 2015 |
Keywords provided by Assistance Publique - Hôpitaux de Paris:
|
Congenital cerebellar ataxias Genetics Gene ATCAY Gene ABC7 Cerebellar atrophy |
Additional relevant MeSH terms:
|
Ataxia Cerebellar Ataxia Spinocerebellar Ataxias Spinocerebellar Degenerations Dyskinesias Neurologic Manifestations Nervous System Diseases Signs and Symptoms |
Cerebellar Diseases Brain Diseases Central Nervous System Diseases Spinal Cord Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn |
ClinicalTrials.gov processed this record on September 21, 2017