Dépistage de l'hypercholestérolémie familiale en Tunisie par séquençage de l'exome entier : Importance dans le diagnostic et la gestion des soins de santé
DOI :
https://doi.org/10.62438/tunismed.v103i4.5359Mots-clés :
Hypercholestérolémie, LDLR, Afrique du Nord, Séquençage de l'exome entier, Analyse bioinformatique, Variant du site d'épissageRésumé
Objectif : Déterminer les variants pathogènes liés à l'hypercholestérolémie familiale (HF) au sein d'une famille du sud de la Tunisie en utilisant le séquençage de l'exome entier (WES).
Méthodes : L'ADN génomique a été extrait du sang total chez le cas index ainsi que chez d'autres membres de la famille, affectés et non affectés. Ensuite, le WES a été réalisé uniquement chez le proband. La pathogénicité des variations génétiques a été évaluée dans un ensemble de 13 gènes rapportés comme associés à l'HF en utilisant des outils de filtrage combiné et de prédiction bioinformatique. Enfin, le séquençage de Sanger a été effectué pour vérifier les mutations probablement pathogènes prédites chez le proband et pour vérifier la ségrégation familiale chez tous les sujets de la famille.
Résultats : Nos résultats ont montré la présence d'une mutation pathogène au niveau du site d'épissage (c.1186+1G>A) dans le gène LDLR chez le proband et d'autres membres affectés de la famille. Le suivi de la famille a révélé l'efficacité de la combinaison de rosuvastatine et d'ézétimibe avec un régime alimentaire sain pour atteindre l'objectif de traitement du LDL-c, avec une diminution d'environ 50 % pour le proband.
Conclusion : Cette étude est la première de son genre à utiliser le WES pour le dépistage et le diagnostic de l'HF en Tunisie. Nous soulignons ici l'importance de l'analyse moléculaire pour une meilleure gestion des soins de santé des patients atteints d'HF et de leurs familles.
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