Kidney Week

Abstract: SA-PO600

Clinical Characterization of Families with Mutations in the MUC-1 Gene

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Bleyer, Anthony J., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States

Anthony J. Bleyer,

• Deltas, Constantinos, University of Cyprus, Nicosia, Cyprus

Constantinos Deltas,

• Papagregoriou, Gregory, University of Cyprus, Nicosia, Cyprus

Gregory Papagregoriou,

• Kmoch, Stanislav, Institute of Inherited Metabolic Disorders, Prague, Czechia

Stanislav Kmoch,

• Kidd, Kendrah O., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States

Kendrah O. Kidd,

• Alper, Seth L., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Seth L. Alper,

• Lavin, Peter J., Trinity Health Kidney Centre, Dublin, Ireland

Peter J. Lavin,

• Gale, Daniel P., University College London, London, United Kingdom

Daniel P. Gale,

• Conlon, Peter J., Beaumont Hospital, Dublin 9, Co Dublin, Ireland

Peter J. Conlon,

• Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States

Peter C. Harris,

• Greka, Anna, Harvard Medical School, Boston, Massachusetts, United States

Anna Greka,

Background

Autosomal dominant tubulo-interstitial kidney disease (ADTKD) due to MUC1 mutations is caused most commonly by a single cytosine insertion within the variable number of tandem repeat (VNTR) region of the MUC1 gene. ~ 30 families have been reported with this condition to date, with considerable variation in the observed age of onset of end stage renal disease (ESRD). We have reevaluated these clinical findings in a larger cohort of families.

Methods

MUC1 mutational analysis was carried out through an assay designed by and offered at no cost to patients or providers at Broad Institute of MIT and Harvard on families with a history of ADTKD. Family histories and pedigrees were clinically characterized. We also included historic data for patients with presumed ADTKD-MUC1 (defined as deceased family members who reached ESRD, and from whom DNA samples were unavailable for mutational analysis).

Results

We identified a MUC1 mutation in 129 families. The mean age of ESRD among individuals was 44.0 ± 13.7 years, with substantial inter- and intrafamilial variation. The mean age of ESRD onset for all families was 41.5 ± 11.5, with a range from 25 to 73.5 years. The mean age of ESRD for families with more than 20 affected members was 50.9 ± 13.0, vs a mean age of ESRD of 41.4 ± 13.1 for families with fewer than 20 affecteds (p < 0.0001). Figure 1 shows the mean age of ESRD onset for 23 largest families, with significant variation in age of ESRD within families.

Conclusion

The mean age of ESRD varies substantially within and among families with ADTKD-MUC1. Larger families have a later mean age of onset of ESRD, likely reflecting milder kidney disease resulting in larger ascertained family size. Further work will aim to identify risk factors for disease severity.

Figure 1. Age of ESRD in individuals according to MUC1 family. Each column represents one of our 23 largest MKD families.

Funding

• Private Foundation Support