Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias (ATAXIC)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 ] [ Designated as safety issue: No ]
- Percentage of patients with severe/moderate/mild/absent intellectual deficiency [ Time Frame: 1 day ] [ Designated as safety issue: No ]
- Percentage of patients with/without epilepsy/spasticity/extraneurological features and nature and frequency of MRI anomalies [ Time Frame: 1 day ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Blood sample
| 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.
Other Name: blood sample
|
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| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
All types
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
No publications provided
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT01488461 History of Changes |
| Other Study ID Numbers: | NI 08034, AOM 09178 |
| Study First Received: | December 6, 2011 |
| Last Updated: | October 7, 2014 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: French Data Protection Authority |
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 Brain Diseases Central Nervous System Diseases Cerebellar Diseases Dyskinesias |
Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Nervous System Diseases Neurodegenerative Diseases Neurologic Manifestations Signs and Symptoms Spinal Cord Diseases |
ClinicalTrials.gov processed this record on February 25, 2015