Journal article
Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1
Clinical journal of the American Society of Nephrology, Vol.9(3), pp.527-535
03/2014
DOI: 10.2215/CJN.06380613
PMCID: PMC3944763
PMID: 24509297
Abstract
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 investigation was to analyze the clinical characteristics of families and individuals with this mutation.
Families with autosomal dominant interstitial kidney disease were 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).
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.
MUC1 mutation results in progressive chronic kidney failure with 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.
Details
- Title: Subtitle
- Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1
- Creators
- Anthony J BleyerDouglas SomersStanislav KmochCorinne AntignacVicki RobinsKendrah KiddJohn R KelsoeGerald HladikPhilip KlemmerStephen J KnohlSteven J ScheinmanNam VoAnn SantiAlese HarrisOmar CanadayNelson WellerPeter J HulickKristen VogelFrederick F Rahbari-OskouiJennifer TuazonConstantinos DeltasAndre MegarbanePaul L KimmelC John SperatiAvi Orr-UrtregerShay Ben-ShacharDavid A WaughStella McGinnAnthony J Bleyer JrKaterina HodanováPetr Vylet'alMartina ŽivnáThomas C HartP Suzanne Hart
- Resource Type
- Journal article
- Publication Details
- Clinical journal of the American Society of Nephrology, Vol.9(3), pp.527-535
- DOI
- 10.2215/CJN.06380613
- PMID
- 24509297
- PMCID
- PMC3944763
- ISSN
- 1555-9041
- eISSN
- 1555-905X
- Grant note
- Intramural NIH HHS
- Language
- English
- Date published
- 03/2014
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094587902771
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