title: Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors: Anthony J
authors: AJ
authors: Bleyer
authors: Stanislav
authors: S
authors: Kmoch
authors: Corinne
authors: C
authors: Antignac
authors: Vicki
authors: V
authors: Robins
authors: Kendrah
authors: K
authors: Kidd
authors: John R
authors: JR
authors: Kelsoe
authors: Gerald
authors: G
authors: Hladik
authors: Philip
authors: P
authors: Klemmer
authors: Stephen J
authors: SJ
authors: Knohl
authors: Steven J
authors: SJ
authors: Scheinman
authors: Nam
authors: N
authors: Vo
authors: Ann
authors: A
authors: Santi
authors: Alese
authors: A
authors: Harris
authors: Omar
authors: O
authors: Canaday
authors: Nelson
authors: N
authors: Weller
authors: Peter J
authors: PJ
authors: Hulick
authors: Kristen
authors: K
authors: Vogel
authors: Frederick F
authors: FF
authors: Rahbari-Oskoui
authors: Jennifer
authors: J
authors: Tuazon
authors: Constantinos
authors: C
authors: Deltas
authors: Douglas
authors: D
authors: Somers
authors: Andre
authors: A
authors: Megarbane
authors: Paul L
authors: PL
authors: Kimmel
authors: C John
authors: CJ
authors: Sperati
authors: Avi
authors: A
authors: Orr-Urtreger
authors: Shay
authors: S
authors: Ben-Shachar
authors: David A
authors: DA
authors: Waugh
authors: Stella
authors: S
authors: McGinn
authors: Anthony J
authors: AJ
authors: Bleyer
authors: Katerina
authors: K
authors: Hodanová
authors: Petr
authors: P
authors: Vylet'al
authors: Martina
authors: M
authors: Živná
authors: Thomas C
authors: TC
authors: Hart
authors: P Suzanne
authors: PS
authors: Hart
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1