Moderate phenotypic expression of familial hypercholesterolemia in Tunisia Awatef Jelassi a , Afef Slimani a , Imen Jguirim a , Mohamed Najah a , AbdelMajid Abid b , Lamia Boughamoura c , Jawhar Mzid d , Moncef Fkih e , Fawzi Maatouk f , Mustapha Rouis g , Mathilde Varret h , Mohamed Naceur Slimane a, ⁎ a Research Unit of Genetic and Biological Factors of Atherosclerosis Faculty of Medecine, Monastir, Tunisia b Clinical Service, National Institute of Nutrition and Food Technology, Tunis, Tunisia c Department of Pediatry, Farhat Hachad Hospital, Sousse, Tunisia d Department of Cardiovascular Diseases, Rouad Hospital, Tunis, Tunisia e Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia f Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir, Tunisia g UMR 7079 Physiologie et Physiopathologie, Université Pierre et Marie Curie-Paris 6, France h INSERM U781, Hopital Necker, Universtié Paris Descartes, Paris, France abstract article info Article history: Received 11 November 2009 Received in revised form 3 February 2010 Accepted 3 February 2010 Available online 6 February 2010 Keywords: Familial hypercholesterolemia Clinical expression of the disease Tunisia Background: Autosomal Dominant Hypercholesterolemia (ADH) is an autosomal dominant disease caused by mutations in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Xanthomas and coronary heart diseases (CHD) at an early age are the major clinical manifestations of the disease. Methods: 16 families with familial hypercholesterolemia from different regions in Tunisia participated in the study. Mutations within the LDLR gene were screened through DNA sequencing. Lipids values were measured by standard enzymatic methods. Results: We present here thirty five homozygotes and fifty six heterozygotes. Homozygotes presented extensive xanthomatosis, variable clinical manifestations of CHD, and total cholesterol levels in males and females of 17.26 ± 4.18 and 17.64 ± 2.59 mmol/L respectively. HDL-cholesterol levels were 0.62 ± 0.24 and 1.00 ± 0.61 mmol/L for males and females, respectively. None of the heterozygotes had tendon xanthomas (except for one female aged 62), eight had corneal arcus, and nine developed CHD mean between 46 and 88 years old. Total cholesterol levels in males and females ranged from 4.60 to 8.90 and from 4.30 to 10.50 mmol/L, respectively. Conclusion: Tunisian FH heterozygotes are characterized by a moderate clinical and biological expression of the disease. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Autosomal Dominant Hypercholesterolemia (ADH, OMIM # 143890) is due to mutations in the low density lipoprotein receptor gene (LDLR) [1], the apolipoprotein B-100 gene (APOB) [2], the proprotein convertase subtilin/kexin type 9 gene (PCSK9) [3], or in other unidentified genes [4]. In the worldwide general population, heterozygote ADH forms are the most frequent with an incidence of 1/500, while homozygote forms are rare (1/10 6 ) [1]. The main cause of ADH is Familial Hypercholesterolemia (FH, OMIM # 606945) defined at the molecular level by the presence of a mutation in the LDLR gene (4). Actually over 1050 mutations in this gene have been reported [5,6] (http://www.ucl.ac.uk/fh and http://www. umd.necker.fr). FH is characterized by an elevation of low density lipoprotein (LDL) cholesterol levels in plasma leading to cholesterol deposits in tendons, skin and coronary arteries. Heterozygote FH patients usually have a twofold increase in total cholesterol and LDL-cholesterol and typically present with cardiovascular disease within their fourth decade. Homozygotes FH patients are characterized by an elevation of LDL-cholesterol, often greater than 15 mmol/L, and if left untreated, by the development of severe atherosclerosis and cardiovascular disease within their third decade [1]. A high frequency of FH among the Tunisian population (1/165) which is related to the high level of consanguinity in this population was reported earlier [7]. Until now, 8 mutations in the LDLR gene were reported in Tunisia [8]. The first study reported a mild phenotype for FH heterozygote patients from central and southern Tunisia [7]. The present study exposes the clinical, biological and molecular features of 91 affected members from 16 Tunisian families and shows that Tunisian FH Clinica Chimica Acta 411 (2010) 735–738 ⁎ Corresponding author. Tel.: +216 73 462 200; fax: +216 73 460 737. E-mail address: naceur.slimene@fmm.rnu.tn (M.N. Slimane). 0009-8981/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2010.02.008 Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim