Long-Read Sequencing of the <i>MUC1</i> VNTR: Genomic Variation, Mutational Landscape, and Its Impact on ADTKD Diagnosis and Progression.

ABSTRACT:

Background

ADTKD-MUC1 is caused by frameshift mutations in MUC1 gene that produce a frameshifted protein (MUC1fs) toxic to kidney cells. The gene's variable number of tandem repeats (VNTR), with high GC content, makes it largely inaccessible to standard sequencing. As a result, both the reference sequence and natural variation in this region remain poorly defined, complicating mutation detection and data interpretation. Standard methods also fail to pinpoint the exact VNTR unit affected, limiting insight into mutation mechanisms and genotype-phenotype correlations.

Methods

We employed Single Molecule, Real-Time (SMRT) sequencing and characterized the genomic sequence of MUC1 in 300 individuals including 279 individuals from 143 families suspected of havi

SUBMITTER: Vrbacka A 

PROVIDER: S-EPMC12458345 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature