Journal Article

Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing

Hechmi, Meriem, Elouej, Sahar, Gharbi, Mariem, Alberico, Federica, Yosra Ben Halima, Melika Ben Ahmed, Mazza, Tommaso, Pezzilli, Serena, Kefi, Rym, Hamza Dallali, Chargui, Mariem, Mercuri, Luana, Jamoussi, Henda, Prudente, Sabrina, Jmel, Haifa, Abdelhak, Sonia, Bahlous, Afaf, Abid, Abdelmajid, Sallem, Om Kalthoum, Trischitta, Vincenzo

2019

Overview

AimsMaturity 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.MethodsWe 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.ResultsFive 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.ConclusionsOur 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.

• Publisher: Springer Nature B.V
• Subject: ABCC8 gene / Autosomal dominant inheritance / Bioinformatics / Diabetes / Diabetes mellitus / Diagnosis / Frameshift mutation / Genetic diversity / Genetic screening / Heredity / Mutation / Next-generation sequencing