Description of a New Simple and Cost-Effective Molecular Testing That Could Simplify MUC1 Variant Detection

Introduction: Patients with autosomal dominant tubulointerstitial kidney disease (ADTKD) usually present with nonspeci fi c progressive chronic kidney disease (CKD) with mild to negative proteinuria and a family history. ADTKDMUC1 leads to the formation of a frameshift protein that accumulates in the cytoplasm, leading to tubulointerstitial damage. ADTKDMUC1 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 speci fi c 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 con fi rmation 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 ADTKDMUC1. Conclusion: We describe a new simple and cost-effective method for molecular testing of ADTKDMUC1. Genetic analyses in our cohort suggest that MUC1 might be the fi rst cause of ADTKD. Increasing the availability of MUC1 diagnosis tools will contribute to a better understanding of the disease and to the development of speci fi c treatments.