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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01488461
Recruitment Status : Completed
First Posted : December 8, 2011
Last Update Posted : June 15, 2015
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

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 or disease Intervention/treatment
Congenital Cerebellar Ataxias Early-onset Cerebellar Ataxias Genetic: 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 :

  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.

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Study Type : Observational
Actual Enrollment : 165 participants
Observational Model: Family-Based
Official Title: Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias
Study Start Date : January 2012
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Group/Cohort Intervention/treatment
patients ataxic Genetic: blood sample
Blood sample will be analysed in order to check presence or not of mutation in ABC7, SLC9A6, GPR56, ATCAY.

Primary Outcome Measures :
  1. Percentage of the patients with a mutation in one of the analysed genes. [ Time Frame: 1 day ]

Secondary Outcome Measures :
  1. Percentage of patients with severe/moderate/mild/absent intellectual deficiency [ Time Frame: 1 day ]
  2. 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
Blood sample

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01488461

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Hôpital Trousseau, Service de Génétique
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Lydie Burglen, PhD Assistance Publique
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Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01488461    
Other Study ID Numbers: NI 08034
AOM 09178 ( Other Identifier: Assistance Publique )
First Posted: December 8, 2011    Key Record Dates
Last Update Posted: June 15, 2015
Last Verified: June 2015
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Congenital cerebellar ataxias
Gene ABC7
Cerebellar atrophy
Additional relevant MeSH terms:
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Cerebellar Ataxia
Spinocerebellar Degenerations
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn