Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias

Congenital Cerebellar Ataxias Clinical Trial

— ATAXIC  

Official title:

Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01488461
• Other study ID #: NI 08034
• Secondary ID: AOM 09178
• Status: Completed
• Phase: N/A
• First received: December 6, 2011
• Last updated: June 12, 2015
• Start date: January 2012
• Est. completion date: October 2014

Study information

• Verified date: June 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: French Data Protection Authority
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Observational Model: Family-Based

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Congenital Cerebellar Ataxias
• Early-onset Cerebellar Ataxias
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Intervention

Genetic:
• blood sample
Blood sample will be analysed in order to check presence or not of mutation in ABC7, SLC9A6, GPR56, ATCAY.

Locations

Country	Name	City	State
France	Hôpital Trousseau, Service de Génétique	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of the patients with a mutation in one of the analysed genes.		1 day	No
Secondary	Percentage of patients with severe/moderate/mild/absent intellectual deficiency		1 day	No
Secondary	Percentage of patients with/without epilepsy/spasticity/extraneurological features and nature and frequency of MRI anomalies		1 day	No