title: Novel mutations in the duplicated region of PKD1 gene.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) exhibits a genetically heterogeneous transmission involving at least three different genes. PKD1 gene linked mutations are responsible for the disease in about 85% of ADPKD cases. The search for mutations is a very important step in understanding the molecular mechanisms underlying ADPKD. We undertook this study using denaturing gradient gel electrophoresis (DGGE), after a stage of long range PCR, to scan for mutations in the duplicated region of the PKD1 gene in French ADPKD families. This allowed us to identify eight novel mutations and several polymorphisms: among the mutations, three are nonsense mutations, two are deletions in the coding sequence leading to frameshift mutations, one is a splice mutation and two are highly probable missense mutations. In this paper, we also provide a review of the mutations reported so far which are widespread throughout the gene. Although no clear hot spot for mutation is apparent, we will focus on some clustering observed.
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU and EFS-Bretagne, Brest, France. regine.perrichot@univ-brest.fr
authors.forename: R
authors.initials: R
authors.lastname: Perrichot
authors.forename: B
authors.initials: B
authors.lastname: Mercier
authors.forename: I
authors.initials: I
authors.lastname: Quere
authors.forename: A
authors.initials: A
authors.lastname: Carre
authors.forename: P
authors.initials: P
authors.lastname: Simon
authors.forename: B
authors.initials: B
authors.lastname: Whebe
authors.forename: J
authors.initials: J
authors.lastname: Cledes
authors.forename: C
authors.initials: C
authors.lastname: Ferec
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D050396:TRPP Cation Channels
chemical_list: D011506:Proteins; D050396:TRPP Cation Channels