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Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.
- Source :
-
Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2014 Mar; Vol. 9 (3), pp. 527-35. Date of Electronic Publication: 2014 Feb 07. - Publication Year :
- 2014
-
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 investigation was to analyze the clinical characteristics of families and individuals with this mutation.<br />Design, Setting, Participants, & Measurements: 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).<br />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.<br />Conclusion: 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.
- Subjects :
- Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
DNA Mutational Analysis
Disease Progression
Female
Gene-Environment Interaction
Genetic Predisposition to Disease
Humans
Kidney physiopathology
Kidney Failure, Chronic genetics
Kidney Failure, Chronic physiopathology
Male
Middle Aged
Pedigree
Phenotype
Polycystic Kidney, Autosomal Dominant complications
Polycystic Kidney, Autosomal Dominant diagnosis
Polycystic Kidney, Autosomal Dominant physiopathology
Registries
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Young Adult
Mucin-1 genetics
Mutation
Polycystic Kidney, Autosomal Dominant genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1555-905X
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical journal of the American Society of Nephrology : CJASN
- Publication Type :
- Academic Journal
- Accession number :
- 24509297
- Full Text :
- https://doi.org/10.2215/CJN.06380613