Dataset Information

Molecular and clinical assessment of maturity-onset diabetes of the young revealed low mutational rate in Moroccan families.

ABSTRACT:

Background

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance. To offer an adequate patient management and therapeutic treatment for MODY patients, in addition to an early efficient diagnosis of their asymptomatic relatives, it is crucial to set an accurate molecular diagnosis. Hence, our aim was to determine the frequency of HNF1A and GCK genes among Moroccan-suspected MODY patients.

Methods

Twenty suspected MODY patients were screened for HNF1A and GCK mutations using Sanger sequencing and MLPA methods. Segregation analysis of identified mutations was performed among family members. The pathogenic nature of missense variants was predicted using bioinformatic tools.

Results

A total of two mutations were revealed among all patients raising the diagnostic rate to 10%. We identified a large novel GCK deletion (c.209-?_1398+?del) by MLPA in one patient and a previously reported missense substitution (c.92G > A) in HNF1A gene.

Conclusion

This is the first investigation to perform the molecular diagnosis of MODY suspected patients. Our findings constitute a primary contribution towards unraveling the genetic landscape involved in the pathogenesis of MODY disease in Morocco.

SUBMITTER: Trhanint S

PROVIDER: S-EPMC9152556 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Molecular and clinical assessment of maturity-onset diabetes of the young revealed low mutational rate in Moroccan families.

Trhanint Said S Bouguenouch Laila L Abourazzak Sana S El Ouahabi Hanan H Latrech Hanane H Benyakhlef Salma S Bennani Bahia B El Bouchikhi Ihssane I Moufid Fatima Zahra FZ Ouldim Karim K El Ghadraoui Lahsen L Maazouzi Nadia N

International journal of pediatrics & adolescent medicine 20210322 2

<h4>Background</h4>Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance. To offer an adequate patient management and therapeutic treatment for MODY patients, in addition to an early efficient diagnosis of their asymptomatic relatives, it is crucial to set an accurate molecular diagnosis. Hence, our aim was to determine the frequency of HNF1A and GCK genes among Moroccan-suspected MODY patients.<h4>Methods</h4>Twenty suspected ...[more]

PMID: 35663783

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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

Molecular and clinical assessment of maturity-onset diabetes of the young revealed low mutational rate in Moroccan families.

Background

Methods

Results

Conclusion

Publications

Molecular and clinical assessment of maturity-onset diabetes of the young revealed low mutational rate in Moroccan families.

Similar Datasets

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