The frameshifted VNTR length determines the kidney survival in ADTKD-MUC1

In 49 genetically confirmed ADTKD-MUC1 patients, longer MUC1-frameshift (MUC1-fs) protein length predicts earlier kidney failure, with median KF-free survival 43 vs 65 years.

• Why it matters: ADTKD-MUC1 has been treated as genotypically uniform despite wide clinical variability, leaving uncertainty about what drives differences in disease severity.
• What they did: Using Oxford Nanopore long-read sequencing to reconstruct mutant VNTR alleles, the study modeled associations between total and MUC1-fs length and age at kidney failure while accounting for familial clustering.
• The result: MUC1-fs length was linked to kidney failure (HR 1.19 per 100 amino acids, p = 0.015) and faster eGFR decline, while total mutant protein length showed weaker or no independent signal.

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