Title: Molecular study for Metabolic Liver Diseases

Biography:

Emna Barkaoui: obtained Pediatric Diploma from Rene Descartes University of Paris V France, Pediatric Hepatology and Gastroenterology Diploma from Angers France, with expertise in pediatric hepatology, and liver metabolic disease, responsible of the pediatric unity, responsible of the pediatric liver transplantation program, member of comity of liver transplantation  in Health Ministry, associated member of the Cellular and Molecular Hematology Laboratory in Pasteur Institute of Tunis, Tunisia, Researcher working on hereditary cholestasis, Glycogenosis type I and Hereditary Tyrosinemia type I, member of Groupe Francophone de Gastroenterologie Hepatologie et Nutrition Pediatrique, Member of MEMG, Magrebian Pediatric Research Award 2006, Poster Award in MEMG 2016, and teaching in hospital.

Abstract

From 2002 to 2016 we studied three diseases glycogenosis storage disaese type Ia (22 Tunisisan cases), progressive intrahepatic cholestasis with normal gammaglutamyl transferasis (13, Tunisian and Libyan cases) and NPC 1(5 Libyan cases).

The Molecular study was done in Tunisian laboratory for GSD using PCR and direct squencing of the G6PC gene and the 2 genes ATP8B1 and ABCB11 for PFIC, and  by Centogen laboratory for Nieman Pick C patients. We used for the first time the splicing Finder Program and Ex-Skip program for the analysis of intronic variants in PFIC patients.

Results : For GSD type Ia : 2 recurrent mutations the R83C and R170Q were found in 90% of patients. For PFIC with normal gammaglutamyltransferase : For ATP8B1, we found Nine exonic mutations, four of them novels and seven novel  intronic. For ABCB11, we found three exonic mutations with two novels  and two novel intronic mutations.

Discussion : Our study  were the first in Tunisia and North Africa for these diseases. For GSD type Ia the R83C and R170Q mutations were found in more than 90% of patients and show a possible founder effect.  For PFIC the results are heterogene but 2 patients had Y354X and dropped their alphafoetoproteine hepatocarcinoma was confirmed in One,  both had a liver transplantation (respectively at age of 6 months and 3 years).  For NPC1 we found 3 novel mutations type encompassing in two patients, a multiple copies of two exons in one patient and a missens mutation .