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 journalArticle

33 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)527-535
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume9
Issue number3
DOIs
StatePublished - Mar 7 2014

Fingerprint

Mucoproteins
Mutation
Chronic Kidney Failure
Age of Onset
Respiratory System
Gastrointestinal Tract
Breast
Distal Kidney Tubule
Medullary cystic kidney disease 1
Kidney
Gene-Environment Interaction
Minisatellite Repeats
Skin
Urinalysis
Cytosine
Genes
Renal Insufficiency
Cysts
Blood Proteins
Dialysis

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Bleyer, Anthony J. ; Kmoch, Stanislav ; Antignac, Corinne ; Robins, Vicki ; Kidd, Kendrah ; Kelsoe, John R. ; Hladik, Gerald ; Klemmer, Philip ; Knohl, Stephen J. ; Scheinman, Steven J. ; Vo, Nam ; Santi, Ann ; Harris, Alese ; Canaday, Omar ; Weller, Nelson ; Hulick, Peter J. ; Vogel, Kristen ; Rahbari-Oskoui, Frederick F. ; Tuazon, Jennifer ; Deltas, Constantinos ; Somers, Douglas ; Megarbane, Andre ; Kimmel, Paul L. ; Sperati, C. John ; Orr-Urtreger, Avi ; Ben-Shachar, Shay ; Waugh, David A. ; Mcginn, Stella ; Bleyer, Anthony J. ; Hodaňová, Katerina ; Vyletal, Petr ; Živná, Martina ; Hart, Thomas C. ; Hart, P. Suzanne. / Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1. In: Clinical Journal of the American Society of Nephrology. 2014 ; Vol. 9, No. 3. pp. 527-535.
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abstract = "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.",
author = "Bleyer, {Anthony J.} and Stanislav Kmoch and Corinne Antignac and Vicki Robins and Kendrah Kidd and Kelsoe, {John R.} and Gerald Hladik and Philip Klemmer and Knohl, {Stephen J.} and Scheinman, {Steven J.} and Nam Vo and Ann Santi and Alese Harris and Omar Canaday and Nelson Weller and Hulick, {Peter J.} and Kristen Vogel and Rahbari-Oskoui, {Frederick F.} and Jennifer Tuazon and Constantinos Deltas and Douglas Somers and Andre Megarbane and Kimmel, {Paul L.} and Sperati, {C. John} and Avi Orr-Urtreger and Shay Ben-Shachar and Waugh, {David A.} and Stella Mcginn and Bleyer, {Anthony J.} and Katerina Hodaňov{\'a} and Petr Vyletal and Martina Živn{\'a} and Hart, {Thomas C.} and Hart, {P. Suzanne}",
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Bleyer, AJ, Kmoch, S, Antignac, C, Robins, V, Kidd, K, Kelsoe, JR, Hladik, G, Klemmer, P, Knohl, SJ, Scheinman, SJ, Vo, N, Santi, A, Harris, A, Canaday, O, Weller, N, Hulick, PJ, Vogel, K, Rahbari-Oskoui, FF, Tuazon, J, Deltas, C, Somers, D, Megarbane, A, Kimmel, PL, Sperati, CJ, Orr-Urtreger, A, Ben-Shachar, S, Waugh, DA, Mcginn, S, Bleyer, AJ, Hodaňová, K, Vyletal, P, Živná, M, Hart, TC & Hart, PS 2014, 'Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1', Clinical Journal of the American Society of Nephrology, vol. 9, no. 3, pp. 527-535. https://doi.org/10.2215/CJN.06380613

Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1. / Bleyer, Anthony J.; Kmoch, Stanislav; Antignac, Corinne; Robins, Vicki; Kidd, Kendrah; Kelsoe, John R.; Hladik, Gerald; Klemmer, Philip; Knohl, Stephen J.; Scheinman, Steven J.; Vo, Nam; Santi, Ann; Harris, Alese; Canaday, Omar; Weller, Nelson; Hulick, Peter J.; Vogel, Kristen; Rahbari-Oskoui, Frederick F.; Tuazon, Jennifer; Deltas, Constantinos; Somers, Douglas; Megarbane, Andre; Kimmel, Paul L.; Sperati, C. John; Orr-Urtreger, Avi; Ben-Shachar, Shay; Waugh, David A.; Mcginn, Stella; Bleyer, Anthony J.; Hodaňová, Katerina; Vyletal, Petr; Živná, Martina; Hart, Thomas C.; Hart, P. Suzanne.

In: Clinical Journal of the American Society of Nephrology, Vol. 9, No. 3, 07.03.2014, p. 527-535.

Research output: Contribution to journalArticle

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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