INTRODUCTION: Patients with autosomal dominant tubulointerstitial kidney disease (ADTKD) usually present with nonspecific progressive chronic kidney disease (CKD) with mild to negative proteinuria and a family history. ADTKD-MUC1 leads to the formation of a frameshift protein that accumulates in the cytoplasm, leading to tubulointerstitial damage. ADTKD-MUC1 prevalence remains unclear because MUC1 variants are not routinely detected by standard next-generation sequencing (NGS) techniques. METHODS: We developed a bioinformatic counting script that can detect specific genetic sequences and count the number of occurrences. We used DNA samples from 27 patients for validation, 11 of them were patients from the Lille University Hospital in France and 16 were from the Wake Forest Hospital, NC. All patients from Lille were tested with an NGS gene panel with our script and all patients from Wake Forest Hospital were tested with the snapshot reference technique. Between January 2018 and February 2023, we collected data on all patients diagnosed with MUC1 variants with this script. RESULTS: A total of 27 samples were tested anonymously by the BROAD Institute reference technique for confirmation and we were able to get a 100% concordance for MUC1 diagnosis. Clinico-biologic characteristics in our cohort were similar to those previously described in ADTKD-MUC1. CONCLUSION: We describe a new simple and cost-effective method for molecular testing of ADTKD-MUC1. Genetic analyses in our cohort suggest that MUC1 might be the first cause of ADTKD. Increasing the availability of MUC1 diagnosis tools will contribute to a better understanding of the disease and to the development of specific treatments.

1st Faculty of Medicine Charles University Nové Město Czechia

Department of Biochemistry and Molecular Biology Institut National de la Santé et de la Recherche Médicale Centre Hospitalier Universitaire de Lille Lille France

Functional and Structural Platform Université de Lille Lille France

Institute of Human Genetics Center for Molecular Medicine Cologne Cologne Germany

Jean Pierre Aubert Research Center University of Lille Lille France

Nephrology Centre Hospitalier Regional Universitaire de Lille Lille France

Neuroscience and Cognition University Lille Inserm CHU Lille Lille France

Section on Nephrology Wake Forest School of Medicine Winston Salem North Carolina USA

Service de Toxicologie et Génopathies CHU Lille Lille France

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