Search

Trabalho desenvolvido na sequência de projeto de colaboração Portugal-Tunisia iniciado no IBMC-UP. [ENG] Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid b-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI)represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members. [FR] Résumé: La maladie de Gaucher est une maladie de surcharge lysosomale due à un déficit de l’enzyme β-glucosidase. Afin d’étudier le spectre mutationnel de cette affection en Tunisie, nous avons recherché les mutations récurrentes chez 30 patients. Le dépistage des mutations récurrentes par PCR/RFLP et séquençage direct a révélé que la mutation N370S est la plus fréquente (44 %, 22/50 allèles mutés), suivie par la mutation L444P qui présente une fréquence de l’ordre de 16 % (8/50 allèles mutés). L’allèle recombinant (RecNciI) a été retrouvé chez 14 % des cas étudiés. Les mutations non identifiées dans cette étude représentent 26 %. En outre, nos résultats ont montré que le génotype N370S/RecNciI est le plus fréquent dans les formes à révélation pédiatrique et il est associé à une atteinte viscérale sévère. La recherche de ces mutations en priorité fournit un outil de diagnostic moléculaire pour la majorité des patients, elle permet ainsi un dépistage des hétérozygotes indispensable pour le conseil génétique. Abstract: Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid β-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.

This work was supported by Grant BD/2299/ 92-ID from JNICT