title: [Heterozygosity loss and somatic mutations in type I and II dominant autosomal renal polycystic kidney disease: evidence of a recessive mechanism at a cell level in cystogenesis].
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder mainly characterized by renal cyst formation. Cysts in ADPKD are focal in nature, since only a small fraction of nephrons become cystic. The hypothesis that a second hit may be required for cyst formation has been proposed. This hypothesis suggests that inactivation of the inherited wild-type allele by a somatic mutation triggers cyst formation. In some cases, this second hit eliminates the normal allele and the affected cells remain with a single allele, which is the inherited mutated copy, and we only visualize one allele after the amplification by polymerase chain reaction; this is called loss of heterozygosity (LOH). In this study we have analysed the DNA isolated from epitehlial cells from 164 cysts of 8 kidneys affected by ADPKD type I and 30 cysts form a kidney affected by ADPKD type II. We have demonstrated the presence of LOH in 20.1% of PKD1 cysts and in 10% of PKD2 cysts. We have also found eight other different mutations in PKD2 cysts without LOH; so the percentage of somatic mutations in the PKD2 kidney reaches 36.6% of cysts. In conclusion, our data suggest that a recessive mechanism at the cellular level is implicated in cyst formation in the PKD1 and the PKD2 disease. The loss of both copies of the gene triggers the proliferation of a single cell, resulting in the cyst formation.
authors.affiliation: Servicio de Nefrología, Hospital Clínic, Barcelona.
authors.forename: L
authors.initials: L
authors.lastname: Pérez-Oller
authors.forename: R
authors.initials: R
authors.lastname: Torra
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: J L
authors.initials: JL
authors.lastname: San Millán
authors.forename: A
authors.initials: A
authors.lastname: Darnell
mesh_terms: D002885:Chromosomes, Human, Pair 16; D002893:Chromosomes, Human, Pair 3; D002894:Chromosomes, Human, Pair 4; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*
vernacular_title: Estudio de pérdidas de heterozigosidad y mutaciones somáticas en la poliquistosis renal autosómica dominante tipos I y II: demostración de un mecanismo recesivo a nivel celular en la cistogénesis.