Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries.
Exome sequencing
Genetic diagnosis
Maturity-onset diabetes of the young (MODY)
Monogenic diabetes
Pathogenic variant
Journal
Diabetes research and clinical practice
ISSN: 1872-8227
Titre abrégé: Diabetes Res Clin Pract
Pays: Ireland
ID NLM: 8508335
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
05
08
2020
revised:
01
11
2020
accepted:
10
11
2020
pubmed:
27
11
2020
medline:
16
3
2021
entrez:
26
11
2020
Statut:
ppublish
Résumé
Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically. To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries. We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data. Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients. Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes.
Sections du résumé
BACKGROUND
BACKGROUND
Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically.
AIMS
OBJECTIVE
To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries.
METHODS
METHODS
We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data.
RESULTS
RESULTS
Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients.
CONCLUSIONS
CONCLUSIONS
Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes.
Identifiants
pubmed: 33242514
pii: S0168-8227(20)30810-X
doi: 10.1016/j.diabres.2020.108553
pii:
doi:
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
108553Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Prof. M. Marre reports personal fees from Abbott, Intarcia, Eli Lilly, MSD, Novo Nordisk, Sanofi and Servier, grants from Novo Nordisk, Sanofi, Servier, MSD and Novartis, and nonfinancial support from Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.