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Étude génétique et corrélation génotype-phénotype de la maladie de Parkinson dans la population tunisienne

Abstract : Tunisia has been a crossroads of multiple civilizations during successive historical periods including the original Berber population to the Arabs and Europeans. This region is characterized by large pedigrees, low migration rates and high rates of consanguinity that increase the risk of autosomal recessive diseases including neurodegenerative diseases. In our country, the prevalence of Parkinson's disease (PD) increases to 43/100000 person and becomes a major health problem. PD affects more than 2% of adults over the age of 60. It is considered to be the result of the interaction between genetic and environmental factors. During the last 20 years, several genes have been linked to hereditary forms of PD in patients who developed their first symptoms before the age of 40. Our findings showed that the Tunisian population is distinct from other populations, as it is striking that more than 50% of all cases have a genetic origin. The frequency of monogenic forms in patients with late onset PD was relatively high and similar to that of patients with early onset. These forms were mainly due to the mutation LRRK2-p.G2019S (identified in 44.4% of cases). We confirmed that this mutation is a founder mutation appeared in a single common ancestor of Berber origin. Clinically, we showed that patients with the LRRK2-p.G2019S mutation had an earlier onset of PD, but with a more benign phenotype than idiopathic. A second founder mutation with a Berber origin (p.Q456*) was identified in the PINK1 gene. The unusual high frequency of mutations in this gene may be limited to the Tunisian Berber population. Our results also confirmed that mutations in the PARK2 gene and the GBA gene do not constitute a frequent risk factor for PD in Tunisia. In addition to these mutations on known genes, we have identified 4 new candidate genes in PD. This particular genetic structure of PD in Tunisia could be mainly the result of the historical Berber origin of our Tunisian population.
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Sawssan Ben Romdhan. Étude génétique et corrélation génotype-phénotype de la maladie de Parkinson dans la population tunisienne. Génétique humaine. Université Paris sciences et lettres; Université de Sfax (Tunisie), 2019. Français. ⟨NNT : 2019PSLEP031⟩. ⟨tel-02899962⟩

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