title: A novel frameshift mutation induced by an adenosine insertion in the polycystic kidney disease 2 (PKD2) gene.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common Mendelian disorders and is genetically heterogeneous. Linkage studies have shown that the majority (approximately 85%) of ADPKD cases are due to mutations in PKD1 on chromosome 16p13.3, while mutations in PKD2 on chromosome 4q21-q23 are thought to account for most of the remaining cases. In this report, we describe the mutation in a large four-generation ADPKD family (TOR-PKD77) which we had mapped to the PKD2 locus by linkage analysis. In this family, we screened for mutations by directly sequencing two nested RT-PCR fragments (PKD2N1 and PKD2N2) that cover approximately 90% of the PKD2 open reading frame. In the affected members, we identified a novel single adenosine insertion (2160InsA) in the PKD2N2 fragment. This mutation occurred in the polyadenosine tract (nt2152-2159) of exon 11 and is predicted to result in a frameshift with premature translation termination of the PKD2 product, polycystin 22, immediately after codon 723. The truncated polycystin 2 is predicted to lack the calcium-binding EF-hand domain and two cytoplasmic domains required for the homodimerization of polycystin 2 with itself and for the heterodimerization of polycystin 2 with polycystin 1.
authors.affiliation: Department of Medicine, Toronto Hospital, Ontario, Canada. ypei@torhosp.toronto.on.ca
authors.forename: Y
authors.initials: Y
authors.lastname: Pei
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Kasenda
authors.forename: A D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: E
authors.initials: E
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Lian
authors.forename: E
authors.initials: E
authors.lastname: Rogovea
authors.forename: S
authors.initials: S
authors.lastname: Somlo
authors.forename: P
authors.initials: P
authors.lastname: St George-Hyslop
mesh_terms: D000241:Adenosine / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D008958:Models, Molecular; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D050396:TRPP Cation Channels
chemical_list: D000241:Adenosine; D017931:DNA Primers; D008565:Membrane Proteins; D050396:TRPP Cation Channels