title: DGGE screening of PKD1 gene reveals novel mutations in a large cohort of 146 unrelated patients.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited renal diseases. ADPKD is a genetically heterogeneous disorder involving at least three different genes. PKD1, the major locus mapped to chromosome 16p13.3 accounts for approximately 85% of ADPKD cases. The search for mutations is a very important step in understanding the molecular mechanisms underlying ADPKD. Despite intense screening by many groups, only a small number of mutations have been described so far. We undertook the first study using denaturing gradient gel electrophoresis (DGGE) to scan for mutations in the non-duplicated region of the PKD1 gene in a large cohort of 146 French unrelated ADPKD patients. We successfully identified novel mutations: 3 are frameshift mutations, 2 nonsense mutations, 2 missense mutations, 1 is an insertion in the frame of 9 nucleotides, 3 intronic variations and several polymorphisms. One of these mutations is the fourth de novo mutation described in this gene. We also describe a family with possible clinical anticipation. DGGE is an effective method for detecting nucleotide changes in the PKD1 gene.
authors.affiliation: Services de Néphrologie, CHU Brest, France. regine.perrichot@univ-brest.fr
authors.forename: R A
authors.initials: RA
authors.lastname: Perrichot
authors.forename: B
authors.initials: B
authors.lastname: Mercier
authors.forename: P M
authors.initials: PM
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D016368:Frameshift Mutation; D005602:France; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels
chemical_list: D004247:DNA; D011506:Proteins; D050396:TRPP Cation Channels