title: Chronic renal failure of unknown origin is caused by HNF1B mutations in 9% of adult patients: a single centre cohort analysis.
abstract: BACKGROUND
  HNF1B gene mutations might be an underdiagnosed cause of nephropathy in adult patients mainly because of their pleomorphic clinical presentations. As most studies are based on paediatric populations, it is difficult to assess the likelihood of finding HNF1B mutations in adult patients and consequently define clinical settings in which genetic analysis is indicated. The aim of this study was the search for mutations in the HNF1B gene in a cohort of unrelated adult patients with nephropathy of unknown aetiology.
  
  
  METHODS
  Patients were tested for the HNF1B gene if they had chronic kidney disease of unknown origin and renal structure abnormalities (RSA) or a positive family history of nephropathy. The HNF1B coding sequence and intron-exon boundaries were analysed by direct sequencing. The search for gene deletions was performed by Multiple Ligation Probe Analysis (MLPA).
  
  
  RESULTS
  Heterozygous mutations were identified in 6 out of 67 screened patients (9.0%) and included two whole gene deletions, one nonsense (p.Gln136Stop), two missense (p.Gly76Cys and p.Ala314Thr) mutations and a frameshift microdeletion (c.384_390 delCATGCAG), the latter two (c.384_390 del and p.Ala314Thr) not ever being reported to date. Mean age of the mutated patients at screening was 48.5 years with a M/F ratio of 2/4. The clinical manifestations of affected patients were extremely pleomorphic, including several urological and extra-renal manifestations.
  
  
  CONCLUSIONS
  Mutations of HNF1B could explain chronic kidney disease in up to 9% of adult patients with a nephropathy of unknown aetiology and RSA: therefore an HNF1B mutation analysis should be considered in this group of patients.
authors.affiliation: Department of Translational Medicine, Nephrology and Transplantation, Hospital 'Maggiore della Carità', Novara, NO, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Musetti
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.forename: Simona
authors.initials: S
authors.lastname: Mellone
authors.forename: Alessia
authors.initials: A
authors.lastname: Pagani
authors.forename: Ileana
authors.initials: I
authors.lastname: Fusco
authors.forename: Alice
authors.initials: A
authors.lastname: Monzani
authors.forename: Mara
authors.initials: M
authors.lastname: Giordano
authors.forename: Piero
authors.initials: P
authors.lastname: Stratta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D007558:Italy; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta
keywords: chronic kidney disease; end-stage renal disease (ESRD); hepatocyte nuclear factor-1β gene (HNF1B); hereditary cystic diseases; renal malformations