Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations

Summary

The autosomal dominant spinocerebellar degenerations are a highly heterogeneous, clinically and genetically, group of rare diseases and of severe evolution. So far, the responsible genes for less than 50% of the cases are known and because of their rarity, there are no phenotype-genotype correlations and well-defined disease history.

The aims of the project are to develop and validate quantitative tools of the cerebellar syndrome and of the spasticity, to establish links between the phenotype and the result of the molecular analysis, to identify new loci/genes responsible for these disorders, and to establish the natural history of the disease according to the genotype.

To this end, a prospective and multicentric study is proposed for recruiting and evaluating, clinically, a cohort of 225 patients; 150 of them are already followed-up in the centers involved. A DNA collection will be set up in order to search for the implication of new loci and genes. A clinico-genetic database will be set up combining data from successive clinical evaluations and those of genotyping.

This strategy will allow access to genetic counselling and molecular diagnosis (positive, presymptomatic or prenatal diagnoses), based on a rational strategy from phenotype-genotype correlations and the information concerning the relative frequency of the genes. The detailed description, with the help of new evaluation tools and of the follow-up of the natural history of the disease according to the genotype, constitutes a crucial step in the design of therapeutical trials in these orphan disorders. Furthermore, the regular follow-up by specialized centers will allow better care of the patients.

Conditions

• Spinocerebellar Ataxias
• Spastic Paraplegias

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  collaborator OTHER

• Institut National de la Santé Et de la Recherche Médicale, France

  lead OTHER_GOV

Principal Investigators

• Alexandra Dürr, MD, PhD · Assistance Publique - Hôpitaux de Paris

• Broussolle Emmanuel, MD, PhD · Hôpitaux Civils de Lyon

• Pierre Labauge, MD, PhD · Hôpitaux de Nîmes

• Cyril Goizet, MD · Hôpitaux de Bordeaux

• Patrick Calvas, MD, PhD · Hôpitaux de Toulouse

• Jean-Philippe Azulay, MD, PhD · Assistance Publique - Hôpitaux de Marseille

• Didier Hannequin, MD, PhD · Hôpitaux de Rouen

• Pierre Pollak, MD, PhD · Hôpitaux de Grenoble

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2005-05-31

Primary Completion

2016-05-31

Completion

2020-05-31

Countries

• France

Study Locations