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01-05-2019 | Maturity-Onset Diabetes of the Young | Original Article

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

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

Published in: Acta Diabetologica | Issue 5/2019

Abstract

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.

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Title: Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing
Authors: Hamza Dallali
Serena Pezzilli
Meriem Hechmi
Om Kalthoum Sallem
Sahar Elouej
Haifa Jmel
Yosra Ben Halima
Mariem Chargui
Mariem Gharbi
Luana Mercuri
Federica Alberico
Tommaso Mazza
Afaf Bahlous
Melika Ben Ahmed
Henda Jamoussi
Abdelmajid Abid
Vincenzo Trischitta
Sonia Abdelhak
Sabrina Prudente
Rym Kefi
Publication date: 01-05-2019
Publisher: Springer Milan
Keywords: Maturity-Onset Diabetes of the Young
Hyperglycemia
Published in: Acta Diabetologica / Issue 5/2019
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-018-01283-5

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