Dataset Information

Maturity-Onset Diabetes of the Young Identified Among Algerian Probands with Early-Onset Diabetes.

ABSTRACT:

Aim

To investigate the prevalence of variants within selected maturity-onset diabetes of the young (MODY)-genes among Algerian patients initially diagnosed with type 1 diabetes (T1D) or type 2 diabetes (T2D), yet presenting with a MODY-like phenotype.

Methods

Eight unrelated patients with early-onset diabetes (before 30 years) and six relatives with diabetes were examined by targeted re-sequencing for variants in genes known to be involved in MODY (HNF1A, GCK, HNF4A, HNF1B, INS, ABCC8, KCNJ1). Clinical data for probands were retrieved from hospital records.

Results

A total of 12 variants were identified, of which three were classified as pathogenic and one as a variant of uncertain clinical significance (VUS). Two of the pathogenic variants were found in GCK (p.Gly261Arg and p.Met210Lys, respectively) in one proband each and the remaining pathogenic variant was found in HNF1B (p.Gly76Cys) in a proband also carrying the VUS in HNF1A (p.Thr156Met).

Conclusion

Variants in known MODY-genes can be the cause of early-onset diabetes in Algerians diagnosed with T1D or T2D among patients presenting with a MODY-like phenotype; thus, genetic screening should be considered.

SUBMITTER: Bouldjennet F

PROVIDER: S-EPMC7733395 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Maturity-Onset Diabetes of the Young Identified Among Algerian Probands with Early-Onset Diabetes.

Bouldjennet Faiza F Gjesing Anette P AP Azzouz Malha M Abderrahman Samir Ait SA El Guecier Amina A Ali Said S Oudjit Brahim B Mennadi-Lacete Farida F Yargui Lyèce L Boudiba Aissa A Chibane Ahcène A Touil-Boukoffa Chafia C Hansen Torben T Raache Rachida R

Diabetes, metabolic syndrome and obesity : targets and therapy 20201208

<h4>Aim</h4>To investigate the prevalence of variants within selected maturity-onset diabetes of the young (MODY)-genes among Algerian patients initially diagnosed with type 1 diabetes (T1D) or type 2 diabetes (T2D), yet presenting with a MODY-like phenotype.<h4>Methods</h4>Eight unrelated patients with early-onset diabetes (before 30 years) and six relatives with diabetes were examined by targeted re-sequencing for variants in genes known to be involved in MODY (<i>HNF1A, GCK, HNF4A, HNF1B, INS ...[more]

PMID: 33324081

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Project description:It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes from T2D. Our results have implications for studies investigating metabolic profiles in complex traits including T2D.

Dataset Information

Maturity-Onset Diabetes of the Young Identified Among Algerian Probands with Early-Onset Diabetes.

Aim

Methods

Results

Conclusion

Publications

Maturity-Onset Diabetes of the Young Identified Among Algerian Probands with Early-Onset Diabetes.

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