title: Testing for the cytosine insertion in the VNTR of the MUC1 gene in a cohort of Italian patients with autosomal dominant tubulointerstitial kidney disease.
abstract: BACKGROUND
  Medullary cystic kidney disease type 1 (MCKD1; OMIM #174000) is a familial progressive tubule-interstitial nephropathy belonging to the recently defined group of autosomal dominant tubulointerstitial kidney diseases (ADTKD).
  
  
  METHODS
  A specific type of cytosine insertion in the extracellular variable number tandem repeat (VNTR) domain of the MUC1 gene causing the disease was tested in a group of 21 families with ADTKD. We identified this type of MUC1 mutation in two families, whose affected members are described in detail in this case report. Affected (ADTKD-MUC1) members developed end-stage renal disease (ESRD) with a higher incidence (p = 0.033) and at a younger age (p = 0.013) than probands with ADTKD but without this type of mutation. All patients with MUC1-associated kidney disease shared a rather unspecific tubule-interstitial laboratory pattern without medullary cysts, leading to ESRD between the age of 33 and 47 years. We were not able to identify any single common extra-renal feature among affected patients, even if they had various comorbidities, which are described in detail.
  
  
  CONCLUSIONS
  We identified this type of MUC1 mutation in 9.5 % of families from an ADTKD Italian cohort; larger studies are needed to better define the criteria for genetic testing for this type of mutation.
authors.affiliation: Department of Translational Medicine, Nephrology and Transplantation, University Piemonte Orientale, Novara, Italy. claudio.musetti@med.uniupo.it.
authors.forename: Claudio
authors.identifier: http://orcid.org/0000-0002-8207-6062
authors.initials: C
authors.lastname: Musetti
authors.affiliation: Laboratory of Genetics, Department of Health Sciences and IRCAD, University Piemonte Orientale, Novara, Italy.
authors.forename: Deepak
authors.initials: D
authors.lastname: Babu
authors.affiliation: Laboratory of Genetics, Department of Health Sciences and IRCAD, University Piemonte Orientale, Novara, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Fusco
authors.affiliation: Laboratory of Genetics, Department of Health Sciences and IRCAD, University Piemonte Orientale, Novara, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Mellone
authors.affiliation: Laboratory of Genetics, Department of Health Sciences and IRCAD, University Piemonte Orientale, Novara, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zonta
authors.affiliation: Department of Translational Medicine, Nephrology and Transplantation, University Piemonte Orientale, Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.affiliation: Department of Translational Medicine, Nephrology and Transplantation, University Piemonte Orientale, Novara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cantaluppi
authors.affiliation: Department of Translational Medicine, Nephrology and Transplantation, University Piemonte Orientale, Novara, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Stratta
authors.affiliation: Laboratory of Genetics, Department of Health Sciences and IRCAD, University Piemonte Orientale, Novara, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Giordano
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003596:Cytosine; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D018396:Mucin-1 / Q000235:genetics*; D016254:Mutagenesis, Insertional; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D003596:Cytosine
keywords: Autosomal-dominant tubule-interstitial kidney disease; MUC1; Malignancy; Medullary cystic kidney disease