Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1

Anthony J. Bleyer, Stanislav Kmoch, Corinne Antignac, Vicki Robins, Kendrah Kidd, John R. Kelsoe, Gerald Hladik, Philip Klemmer, Stephen J. Knohl, Steven J. Scheinman, Nam Vo, Ann Santi, Alese Harris, Omar Canaday, Nelson Weller, Peter J. Hulick, Kristen Vogel, Frederick F. Rahbari-Oskoui, Jennifer Tuazon, Constantinos DeltasDouglas Somers, Andre Megarbane, Paul L. Kimmel, C. John Sperati, Avi Orr-Urtreger, Shay Ben-Shachar, David A. Waugh, Stella Mcginn, Anthony J. Bleyer, Katerina Hodaňová, Petr Vyletal, Martina Živná, Thomas C. Hart, P. Suzanne Hart

Research output: Contribution to journalArticlepeer-review


Background and objectives The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigationwas to analyze the clinical characteristics of families and individuals with this mutation. Design, setting, participants, & measurements Families with autosomal dominant interstitial kidney diseasewere referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). Results Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to.80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. ConclusionMUC1 mutation results in progressive chronic kidney failurewith a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

Original languageEnglish
Pages (from-to)527-535
Number of pages9
JournalClinical journal of the American Society of Nephrology : CJASN
Issue number3
StatePublished - 7 Mar 2014
Externally publishedYes


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