TY - JOUR
T1 - Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1
AU - Bleyer, Anthony J.
AU - Kmoch, Stanislav
AU - Antignac, Corinne
AU - Robins, Vicki
AU - Kidd, Kendrah
AU - Kelsoe, John R.
AU - Hladik, Gerald
AU - Klemmer, Philip
AU - Knohl, Stephen J.
AU - Scheinman, Steven J.
AU - Vo, Nam
AU - Santi, Ann
AU - Harris, Alese
AU - Canaday, Omar
AU - Weller, Nelson
AU - Hulick, Peter J.
AU - Vogel, Kristen
AU - Rahbari-Oskoui, Frederick F.
AU - Tuazon, Jennifer
AU - Deltas, Constantinos
AU - Somers, Douglas
AU - Megarbane, Andre
AU - Kimmel, Paul L.
AU - Sperati, C. John
AU - Orr-Urtreger, Avi
AU - Ben-Shachar, Shay
AU - Waugh, David A.
AU - Mcginn, Stella
AU - Bleyer, Anthony J.
AU - Hodaňová, Katerina
AU - Vyletal, Petr
AU - Živná, Martina
AU - Hart, Thomas C.
AU - Hart, P. Suzanne
PY - 2014/3/7
Y1 - 2014/3/7
N2 - 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.
AB - 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.
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U2 - 10.2215/CJN.06380613
DO - 10.2215/CJN.06380613
M3 - Article
C2 - 24509297
AN - SCOPUS:84896813347
SN - 1555-9041
VL - 9
SP - 527
EP - 535
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 3
ER -