Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries

Vaxillaire, Martine; Bonnefond, Amélie; Liatis, Stavros; Hachmi, L. Ben Salem; Jotić, Aleksandra; Boissel, Mathilde; Gaget, Stefan; Durand, Emmanuelle; Vaillant, Emmanuel; Derhourhi, Mehdi; Canouil, Mickaël; Larcher, Nicolas; Allegaert, Frédéric; Medlej, R; Chadli, Asma; Belhadj, Azzedine; Chaïeb, M.; Raposo, Joao-Felipe; İlkova, Hasan; Loizou, Doros; Lalić, Nebojša; Vassallo, Josanne; Marre, Michel; Froguel, Philippe

doi:10.1016/j.diabres.2020.108553

Cited by 8 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…But, we exclude unintentionally carriers of pathogenic/likely pathogenic variants within the most common MODY genes (HNF4A and HNF1A) (91,92). Recently, Vaxillaire et al (21) analyzed a cohort of Mediterranean patients suspected with monogenic diabetes and observed that carriers of pathogenic variants had the lowest BMI. This is not the first study in Tunisia that describes the genetic etiology of MODY/monogenic diabetes in patients with early- onset diabetes.…”

Section: Clinical Exome Sequencing and Variants Detectionmentioning

confidence: 99%

“…Overall, 89 unrelated MODY suspected Tunisian participants (including this study) have been investigated using targeted gene panel sequencing, direct/indirect sequencing, or MLPA testing. Only eleven heterozygous pathogenic variants were found in sixteen unrelated patients (~18%) (16,18,20,21). The results of this study support previous observations of Vaxillaire et al (21) such as (i) the severity of the clinical presentation of non-European cases (including those of Tunisian ancestry) with early-onset diabetes (similar to F2-IV.12 and F4-IV.8 index cases), and (ii) low mutation rates despite the heterogeneous clinical inclusion criteria [although strict in our study (Figure 1)].…”

Section: Clinical Exome Sequencing and Variants Detectionmentioning

confidence: 99%

“…Only eleven heterozygous pathogenic variants were found in sixteen unrelated patients (~18%) (16,18,20,21). The results of this study support previous observations of Vaxillaire et al (21) such as (i) the severity of the clinical presentation of non-European cases (including those of Tunisian ancestry) with early-onset diabetes (similar to F2-IV.12 and F4-IV.8 index cases), and (ii) low mutation rates despite the heterogeneous clinical inclusion criteria [although strict in our study (Figure 1)]. In general, this study supports the hypothesis that Tunisian patients have other forms of monogenic diabetes with largely unknown genetic determinants.…”

Section: Clinical Exome Sequencing and Variants Detectionmentioning

confidence: 99%

“…( 20 ) studied 11 suspected MODY patients and identified five heterozygous pathogenic variants in four patients { GCK p.Arg191Trp, HNF1A c.710A>G, adenosine triphosphate (ATP)-binding cassette, sub-family, member 8 ( ABCC8 ) [(c.2376delC and c.4608+4A>G found at compound heterozygous state) and c.4606G>A]}. Another study has also reported two pathogenic variants in HNF1A (c.476G>A) and HNF4A (c.763C>T) genes ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tunisian Maturity-Onset Diabetes of the Young: A Short Review and a New Molecular and Clinical Investigation

et al. 2021

View full text Add to dashboard Cite

Introduction/AimsMaturity-Onset Diabetes of the Young (MODY) is a monogenic non-autoimmune diabetes with 14 different genetic forms. MODY-related mutations are rarely found in the Tunisian population. Here, we explored MODY related genes sequences among seventeen unrelated Tunisian probands qualifying the MODY clinical criteria.Materials and MethodsThe GCK and HNF1A genes were systematically analyzed by direct sequencing in all probands. Then, clinical exome sequencing of 4,813 genes was performed on three unrelated patients. Among them, 130 genes have been reported to be involved in the regulation of glucose metabolism, β-cell development, differentiation and function. All identified variants were analyzed according to their frequencies in the GnomAD database and validated by direct sequencing.ResultsWe identified the previously reported GCK mutation (rs1085307455) in one patient. The clinical features of the MODY2 proband were similar to previous reports. In this study, we revealed rare and novel alterations in GCK (rs780806456) and ABCC8 (rs201499958) genes with uncertain significance. We also found two likely benign alterations in HNF1A (rs1800574) and KLF11 (rs35927125) genes with minor allele frequencies similar to those depicted in public databases. No pathogenic variants have been identified through clinical exome analysis.ConclusionsThe most appropriate patients were selected, following a strict clinical screening approach, for genetic testing. However, the known MODY1-13 genes could not explain most of the Tunisian MODY cases, suggesting the involvement of unidentified genes in the majority of Tunisian affected families.

show abstract

Section: Clinical Exome Sequencing and Variants Detectionmentioning

confidence: 99%

Section: Clinical Exome Sequencing and Variants Detectionmentioning

confidence: 99%

Section: Clinical Exome Sequencing and Variants Detectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tunisian Maturity-Onset Diabetes of the Young: A Short Review and a New Molecular and Clinical Investigation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Monogenic diabetes (MD) accounts for 1–6% of all cases of diabetes in patients of pediatric-adolescent age, but its prevalence is probably underestimated [ 1 , 2 ]. The most common type of MD is maturity-onset diabetes of the young (MODY), a clinically and genetically heterogeneous group of monogenic, non-insulin-dependent, and nonketotic diabetes mellitus characterized by early onset (commonly before age 25), the absence of autoimmunity, and beta-cell dysfunction [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

et al. 2021

View full text Add to dashboard Cite

Monogenic diabetes (MD) represents a heterogeneous group of disorders whose most frequent form is maturity-onset diabetes of the young (MODY). MD is predominantly caused by a mutation in a single gene. We report a case of a female patient with suspected MD and a positive family history for diabetes and obesity. In this patient, two gene variants have been identified by next-generation sequencing (NGS): one in the Glucokinase (GCK) gene reported in the Human Gene Mutation Database (HGMD) and in the literature associated with GCK/MODY, and the other in the hepatocyte nuclear factor 1A (HNF1A) gene not previously described. The GCK variant was also identified in the hyperglycemic father, whereas the HNF1A variant was present in the mother. This new case of digenic GCK/HNF1A variants identified in a hyperglycemic subject, evidences the importance of NGS analysis in patients with suspected MD. In fact, this methodology will allow us to both increase the number of diagnoses and to identify mutations in more than one gene, with a better understanding of the genetic cause, and the clinical course, of the disease.

show abstract

New results for monogenic diabetes with analysis of causative genes using next-generation sequencing: a tertiary centre experience from Turkey

Karakılıç

Saygılı

Sılan

et al. 2021

Int J Diabetes Dev Ctries

View full text Add to dashboard Cite

Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries

Cited by 8 publications

References 46 publications

Tunisian Maturity-Onset Diabetes of the Young: A Short Review and a New Molecular and Clinical Investigation

Tunisian Maturity-Onset Diabetes of the Young: A Short Review and a New Molecular and Clinical Investigation

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

New results for monogenic diabetes with analysis of causative genes using next-generation sequencing: a tertiary centre experience from Turkey

Contact Info

Product

Resources

About