title: Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background.
  
  
  METHODS
  Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother.
  
  
  CONCLUSIONS
  We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.
authors.affiliation: Institute of Biology and Medical Genetics of the 1st Faculty of Medicine and General Teaching Hospital, Charles University, Albertov 4, Prague 2 128 00, Czech Republic. jreiterova@seznam.cz
authors.forename: Jana
authors.initials: J
authors.lastname: Reiterová
authors.forename: Jitka
authors.initials: J
authors.lastname: Štekrová
authors.forename: Miroslav
authors.initials: M
authors.lastname: Merta
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kotlas
authors.forename: Veronika
authors.initials: V
authors.lastname: Elišáková
authors.forename: Petr
authors.initials: P
authors.lastname: Lněnička
authors.forename: Marie
authors.initials: M
authors.lastname: Korabečná
authors.forename: Milada
authors.initials: M
authors.lastname: Kohoutová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Tesař
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics*
chemical_list: D050396:TRPP Cation Channels