Résumé :
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Early-Onset Torsion Dystonia (EOTD) are rare movement disorders developing in childhood with a neurological origin. They begin in a limb and potentially spread to other parts of the body to become generalized. Molecular defect is known for only a subgroup, consisting of a unique and recurrent mutation (c.907delGAG) in the TOR1A gene. Although the molecular cause of this particular form of EOTD is well known, there is very little epidemiologic data regarding mutation carriers. We first investigated the incidence at birth of the mutation in a population of 12,000 newborns from South- Eastern France and found only one positive. Our results suggest that the prevalence of the disease in France is in the lowest estimations, compared to previous epidemiological surveys (about 1/10,000 to 1/30,000 among non-Jews). We then undertook the census of French TOR1A-mutation carriers and the assessment of clinically associated signs to realize an overview of this population. Collaborations were established between the French laboratories involved in the molecular diagnosis of TOR1A-linked dystonia (Lille, Lyon, Paris and Montpellier). Family history, clinical data and DNA samples were gathered for each of the 53 identified index cases and for their relatives. From these data, we estimate disease frequency to be at least 0.13:100,000 and mutation frequency of 0.17:100,000 in France. Haplotypes linked to the c.907delGAG TOR1A mutation were constructed based on the analysis of flanking microsatellites. The previously reported Ashkenazi-Jewish haplotype, known to be linked with a founder effect, was found in 11 families. Only three of the remaining unrelated families shared the same haplotype suggesting that the mutation probably occurred independently several times in the French population. Finally, it was the first exhaustive nation-wide study of a genetically ascertained population of TOR1A carriers. Our results confirm the scarcity of this disease in the French population.
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