title: Autosomal dominant medullary cystic disease: a disorder with variable clinical pictures and exclusion of linkage with the NPH1 locus.
abstract: BACKGROUND
  The nephronophthisis-medullary cystic disease (NPH/MCD) complex represents a heterogeneous group of hereditary tubulointerstitial nephritis. The most common variant is juvenile recessive NPH, for which a gene locus (NPH1) has been mapped on chromosome 2q13. MCD is a less common dominant condition usually recognized later in life, which resembles NPH in many aspects, still presenting remarkable clinical differences. Nothing is known about the chromosome locus of MCD.
  
  
  METHODS
  Five MCD families were studied. Diagnosis was made by inference from family history, type of inheritance, clinical signs and histology. Multipoint linkage analysis was performed by markers D2S293, D2S340 and D2S160 spanning the entire NPH1 locus.
  
  
  RESULTS
  Diagnosis of MCD was made in 28 affected members (16 males; 12 females), belonging to five families. Histological diagnosis was available in 10 patients; clinical diagnosis in 11; seven deceased relatives had diagnosis of chronic nephritis. The age at diagnosis ranged from 8 to 65 years. Renal medullary cysts were found in a minority of patients. In family 1, the disease was associated with hyperuricaemia and gouty arthritis. Progression of renal disease presented intra- and extra-family variability with members of the same family showing mild elevation of creatinine or terminal renal failure. The NPH1 locus associated to recessive NPH was excluded from linkage to the dominant MCD.
  
  
  CONCLUSIONS
  MCD might be more common than previously assumed. Variability in clinical presentation and absence of histopathological hallmarks contribute to make the diagnosis uncommon. The most remarkable clinical difference with NPH is the age of onset in some kindreds and a delayed progression towards renal failure. The exclusion of linkage to the NPH1 locus suggests the existence of an MCD responsible locus, still to be mapped.
authors.affiliation: Division and Chair of Nephrology, Spedali Civili and University, Brescia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Scolari
authors.forename: G M
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: G
authors.initials: G
authors.lastname: Casari
authors.forename: A
authors.initials: A
authors.lastname: Amoroso
authors.forename: D
authors.initials: D
authors.lastname: Puzzer
authors.forename: G L
authors.initials: GL
authors.lastname: Caridi
authors.forename: B
authors.initials: B
authors.lastname: Valzorio
authors.forename: R
authors.initials: R
authors.lastname: Tardanico
authors.forename: V
authors.initials: V
authors.lastname: Vizzardi
authors.forename: S
authors.initials: S
authors.lastname: Savoldi
authors.forename: B F
authors.initials: BF
authors.lastname: Viola
authors.forename: N
authors.initials: N
authors.lastname: Bossini
authors.forename: E
authors.initials: E
authors.lastname: Prati
authors.forename: R
authors.initials: R
authors.lastname: Gusmano
authors.forename: R
authors.initials: R
authors.lastname: Maiorca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001059:Apoproteins / Q000235:genetics; D029681:Arabidopsis Proteins; D002648:Child; D002889:Chromosomes, Human, Pair 2; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D017809:Fatal Outcome; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology; D007679:Kidney Medulla / Q000002:abnormalities*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D012189:Retrospective Studies
chemical_list: D001059:Apoproteins; D029681:Arabidopsis Proteins; D017931:DNA Primers; D010750:Phosphoproteins; D004247:DNA; C103646:NPH1 protein, Arabidopsis; D017346:Protein Serine-Threonine Kinases