1. Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing
- Author
-
Sonia Abdelhak, Henda Jamoussi, Melika Ben Ahmed, Mariem Gharbi, Haifa Jmel, Abdelmajid Abid, Federica Alberico, Om Kalthoum Sallem, Afaf Bahlous, Hamza Dallali, Rym Kefi, Tommaso Mazza, Serena Pezzilli, Sahar Elouej, Luana Mercuri, Yosra Ben Halima, Mariem Chargui, Sabrina Prudente, Meriem Hechmi, Vincenzo Trischitta, Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National des Sciences Appliquées et de Technologie - Carthage (INSAT Carthage), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), CHU Fattouma Bourguiba [Monastir] (HFB), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage, Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Laboratoire central de biologie médicale, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut National de Nutrition et de Technologie Alimentaire (Tunis) (INNTA), This work was supported by Institut Pasteur of Tunis (PCI-15) and the Tunisian Ministry of higher Education and Scientific Research (LR11 IPT05). This study was partly supported by the Italian Ministry of Health ('Ricerca Corrente 2015–2017' to S. Prudente)., We thank the patients, their parents and healthcare professionals who participated in this study. We also thank the CSS-Mendel Institute (Rome, Italy) for the collaboration and the provision of infrastructure for this research., and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]
- Subjects
Male ,Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,030204 cardiovascular system & hematology ,0302 clinical medicine ,Endocrinology ,Hepatocyte Nuclear Factor 1-alpha ,Frameshift Mutation ,MESH: Heterozygote ,Genetics ,medicine.diagnostic_test ,MESH: Genetic Testing ,MESH: Frameshift Mutation ,High-Throughput Nucleotide Sequencing ,General Medicine ,Targeted gene sequencing ,3. Good health ,HNF1A ,Pedigree ,MESH: Diabetes Mellitus, Type 2/genetics ,Phenotype ,MODY ,Genetic testing ,Next-generation sequencing ,Adult ,Diabetes Mellitus, Type 2 ,Female ,Genetic Testing ,Heterozygote ,Humans ,Mutation ,Tunisia ,MESH: Tunisia ,Prioritization ,MESH: Mutation ,MESH: Pedigree ,030209 endocrinology & metabolism ,Biology ,MESH: Phenotype ,DNA sequencing ,Maturity onset diabetes of the young ,Frameshift mutation ,03 medical and health sciences ,MESH: Diabetes Mellitus, Type 2/diagnosis ,Internal Medicine ,medicine ,Gene ,MESH: Hepatocyte Nuclear Factor 1-alpha/genetics ,Monogenic Diabetes ,MESH: Humans ,MESH: Adult ,medicine.disease ,MESH: Male ,MESH: Female ,MESH: High-Throughput Nucleotide Sequencing ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; AIMS: Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern. The diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of next-generation sequencing in the Tunisian population.METHODS: We performed a targeted sequencing of 27 genes known to cause monogenic diabetes in 11 phenotypically suspected Tunisian patients. We retained genetic variants passing filters of frequency in public databases as well as their probable effects on protein structures and functions evaluated by bioinformatics prediction tools.RESULTS: Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice-site variants were identified in ABCC8 gene.CONCLUSIONS: Our study is the first to investigate the clinical application of targeted next-generation sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population.
- Published
- 2018