NCT04700813

Research Study for Rare Pathogenic Mutations Causing Type 2 Diabetes and Complications

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 4,000 (estimated)
• Sponsor: University of Liege · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Single-center trial The goal is to better understand the various genetic mutations encountered in cases of type 2 diabetes as well as their frequency of occurrence in the population. Such analyzes also make it possible to develop personalized medicine and to be able to prevent the associated risks. The aim of this work is also to demonstrate the value of a systematic genetic diagnosis of patients with DMT2 in order to improve their clinical management. Taking a blood sample, which will consist of the single sample from the entire study (1 single visit, combined with a follow-up visit to the patient's usual diabetist). Participation in this study would make it possible to diagnose rare pathogenic mutations in type 2 diabetes and therefore to be able to adapt the treatment in a specific and personal way depending on the presence or not of the mutations and also to prevent the appearance of other pathologies.

Detailed description

Procedure and methodology: during a follow-up visit to their usual diabetist (at CHU de Liège), we will send each potential volunteer, fulfilling the conditions for inclusion, an information and consent form relating to genetic analyzes. Participation in the protocol is voluntary, after detailed information and discussion with the patient. Once the participation agreement has been obtained, we will take a blood sample, which will be the only sample from the entire study. All the tubes will be centrifuged, decanted, separated and frozen at -80 °C at the CHU de Liège for constitution of a serum bank on site, and of a DNA library at UMR8199. For DNA extraction, samples will be sent at -80 ° C. DNA extraction will be automated (Autopure, Qiagen). After DNA extraction, the genes involved in monogenic diabetes (Table 1) will be sequenced via Twist or NimbleGen capture in combination with Illumina sequencing (NovaSeq 6000), as recommended by Twist, NimbleGen and Illumina. The target will also include genes involved in the rare forms of metabolic diseases associated with diabetes: obesity, metabolic syndrome, familial hypercholesterolemia, kidney disease, cardiovascular disease and non-alcoholic fatty liver disease. This will help refine the patient's phenotypic understanding and improve their care. Table 1. List of genes involved in monogenic diabetes Gene ID NM ID ABCC8 NM\_000352.4 APPL1 NM\_012096.2 BLK NM\_001715.2 CEL NM\_001807.4 DNAJC3 NM\_006260.4 DYRK1B NM\_004714.2 EIF2AK3 NM\_004836.5 FOXP3 NM\_014009.3 GATA4 NM\_002052.3 GATA6 NM\_005257.5 GCK NM\_000162.3 GLIS3 NM\_152629.3 HNF1A NM\_000545.5 HNF1B NM\_000458.3 HNF4A NM\_175914.4 IER3IP1 NM\_016097.4 INS NM\_000207.2 KCNJ11 NM\_000525.3 KLF11 NM\_003597.4 LRBA NM\_6726.4 MAFA NM\_201589.3 MNX1 NM\_005515.3 MRAP2 NM\_138409.3 NEUROD1 NM\_002500.4 NEUROG3 NM\_020999.3 NKX2-2 NM\_002509.3 PAX4 NM\_006193.2 PAX6 NM\_000280.4 PCBD1 NM\_000281.3 PDX1 NM\_000209.3 PPP1R15B NM\_032833.4 PTF1A NM\_178161.2 RFX6 NM\_173560.3 SLC19A2 NM\_006996.2 SLC2A2 NM\_000340.1 STAT3 NM\_139276.2 TRMT10A NM\_152292.4 WFS1 NM\_006005.3 ZFP57 NM\_001109809.2 Following sequencing, mutations will be detected and annotated according to the bioinformatics protocol implemented and optimized in UMR8199 since 2009. Clinical and medical data will also be collected: weight, height, blood pressure, drug treatment, medical and surgical history as well as any other important medical information concerning the subject of the project. Data concerning the patient's ethnic origin will also be collected.

Conditions

• Diabete Type 2

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	search for rare pathogenic mutations	search for rare pathogenic mutations causing diabetes type 2

Timeline

• Start date: 2019-09-13
• Primary completion: 2021-09-30
• Completion: 2021-09-30
• First posted: 2021-01-08
• Last updated: 2021-01-08

Locations

1 site across 1 country: Belgium