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MUC1

For clinicians

A four-step pathway.

Most families with ADTKD-MUC1 have already been evaluated — often repeatedly, sometimes with a biopsy. What is usually missing is not effort but a test capable of reading the region where the variant lives.

  1. 01

    Recognize the pattern

    Unexplained CKD, bland sediment, dominant family history, unremarkable imaging.

    One affected first-degree relative plus a bland sediment is enough to justify the next step. You do not need a biopsy, and a biopsy will not answer the question.

  2. 02

    Do not stop at a standard panel

    Clinically available multigene panels identify fewer than 1% of MUC1 variants.

    A negative kidney gene panel is the most common reason these families go undiagnosed for decades. Read the negative result as incomplete, not reassuring.

  3. 03

    Order VNTR-aware MUC1 testing

    Targeted assays read the cytosine tract that short-read sequencing cannot resolve.

    Research laboratories perform targeted analysis of the 7-cytosine tract, long-read SMRT sequencing, and VNTR amplicon sequencing. Academic ADTKD programmes accept referrals for this testing, in many cases without charge to the family; GeneReviews lists current laboratories and contacts.

  4. 04

    Enroll the family, not just the patient

    A result reclassifies at-risk relatives and opens registry and trial access.

    Cascade testing changes surveillance for siblings and children, and identifies living related donors who should be excluded. Patients already on dialysis or transplanted still benefit — their relatives have not yet been screened.

Testing

Assays that can actually see the variant

Each of these is designed to read through the VNTR. None of them are what a standard renal gene panel runs.

Targeted cytosine-tract analysis

A dedicated assay for the 7-cytosine tract in the MUC1 VNTR, where the great majority of pathogenic insertions sit. The highest-yield first test when ADTKD-MUC1 is specifically suspected.

Long-read SMRT sequencing

Single-molecule reads span the repeat region intact, resolving variants that short-read alignment cannot place. Detects insertions outside the canonical tract.

VNTR amplicon sequencing

Amplification and deep sequencing of the repeat array itself, used to characterise variants and confirm segregation within a family.

MUC1-fs immunohistochemistry

Staining for the frameshifted protein — described on kidney tissue and on non-invasive samples — offers supportive evidence where sequencing access is limited.

Before you refer

What is worth having in hand

A three-generation pedigree

Ages at kidney failure, ages at death, dialysis and transplant history, and any relative told they had “kidney disease of unknown cause”. Note gout: early gout points toward UMOD rather than MUC1, though neither is excluded by its absence.

The negative results

Prior panels, exomes, and biopsy reports. They are not wasted work — they exclude the alternatives and document that the VNTR was never covered. Bring the eGFR trajectory too; its linearity is itself informative.

Diagnosis, testing selection, and family counselling should be coordinated with a nephrologist and a clinical geneticist. The GeneReviews chapter on ADTKD-MUC1 maintains the current list of laboratories and research programmes, and is the single best starting point.