Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias (ATAXIC)

This study has been completed.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris Identifier:
First received: December 6, 2011
Last updated: June 12, 2015
Last verified: June 2015

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

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Percentage of the patients with a mutation in one of the analysed genes. [ Time Frame: 1 day ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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.

Detailed Description:

All patients will be examined by a geneticist or a neuropediatric. All clinical data will be collected.

Strategy of the molecular study :

  1. for all multiplex and consanguineous families a linkage analysis (loci ATCAY and ABC7 and others AC known genes) will be performed.
  2. 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.
  3. For all sporadic male patients and linked families : sequencing of all coding exons of the gene ABC7.
  4. For all patients with suggestive features : sequencing of all coding exons of the gene GPR56, VLDLR, NHE6 or other candidate gene.
  5. In consanguineous families : linkage analysis using SNP-array and analysis of candidate genes present in the regions of extended homozygosity
  6. linkage analysis in dominant families and analysis of candidate genes in the linked regions.
  7. If a new AC locus is identified (using linkage or CGH array), this gene will be sequenced in all patients.

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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
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Please refer to this study by its identifier: NCT01488461

Hôpital Trousseau, Service de Génétique
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: Lydie Burglen, PhD Assistance Publique
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01488461     History of Changes
Other Study ID Numbers: NI 08034  AOM 09178 
Study First Received: December 6, 2011
Last Updated: June 12, 2015
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
Gene ABC7
Cerebellar atrophy

Additional relevant MeSH terms:
Cerebellar Ataxia
Spinocerebellar Ataxias
Spinocerebellar Degenerations
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Signs and Symptoms
Spinal Cord Diseases processed this record on May 23, 2016