ADTKD-MUC1-Diagnostics with VNtyper

Fast ans accurate genotyping of the MUC1 gene from genetic sequence data

February 5, 2025 - Diagnosing ADTKD-MUC1 is a challenge. To make this easier, a special computer program was developed: VNtyper. This article explains how this method works.

WHAT IS VNtyper?

VNtyper is a computer program specifically designed to detect common variants in the MUC1 gene associated with ADTKD-MUC1 (Autosomal Dominant Tubulointerstitial Kidney Disease, MUC1 subtype). The MUC1 gene is located in a highly repetitive region (“VNTR”) and has a very high GC content, which makes analysis using standard methods difficult. VNtyper 2.0 uses specialized algorithms and is available both for local installation (such as in research laboratories) and online at vntyper.org.

WHAT CAN IT BE USED FOR?

Using VNtyper, based on standard sequencing data (short-read sequencing) from routine diagnostics (e.g., for sequencing the other ADTKD genes UMOD, HNF1B, REN, and SEC61A1; or for other kidney diseases), the typical changes (mutations) in the MUC1 gene can be specifically identified. The tool thus enables rapid and reliable screening for ADTKD-MUC1, without the need for costly or particularly complex specialized analysis. The results are compiled into clearly structured reports, allowing for easy interpretation of the findings by physicians and laboratories. Because it is a screening method, the result must always be confirmed by a second, independent test.

WHO IS IT INTENDED FOR?

VNtyper is primarily intended for laboratories, scientists, and nephrologists seeking to diagnose or investigate ADTKD-MUC1. Even smaller institutions or teams that have had little experience with genetic diagnostics to date can benefit from this tool, as an easy-to-use online version is available. In the long term, VNtyper could establish itself as a practical method for MUC1 screening from routine genetic tests and accelerate the diagnosis in patients with suspected ADTKD-MUC1.

CURRENT VALIDATION AND LARGE-SCALE APPLICATION IN ADTKD-Net

VNtyper 2.0 is currently being evaluated using reference datasets from the European research network ADTKD-Net, which is coordinated by the Department of Nephrology at the Charité in Berlin (www.ejprarediseases.org/adtkd-net). In a subsequent step, the tool will be used to screen large groups of patients with chronic kidney disease for MUC1 variants that could be the cause of their condition. ADTKD-Net, which was developed as part of a project funded by the European Joint Programme on Rare Diseases (EJP RD), is expected to significantly advance diagnostic evaluation and future therapeutic trials for ADTKD.

Note: As with all screening procedures, it is important to follow up on positive or inconclusive findings with additional testing—such as in-depth genetic counseling.

Dr. Bernt Popp, BIH Charité – Universitätsmedizin Berlin

Source:

Saei H et al. VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease. Science 2023 Jun 17;26(7):107171

https://pmc.ncbi.nlm.nih.gov/articles/PMC10338300/Die Diagnose von ADTKD-MUC1 ist eine Herausforderung. Um dies zu erleichtern, wurde ein spezielles Computerprogramm entwickelt: VNtyper. In diesem Beitrag wird erklärt, wie diese Methode funktioniert.