Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsReynolds, D M
Watnick, T J
Lens, X M
Breuning, M H
Germino, G G
Peters, D J
MetadataShow full item record
CitationJ Am Soc Nephrol. 1999, 10(11):2342-51
AbstractIt is estimated that approximately 15% of families with autosomal dominant polycystic kidney disease (ADPKD) have mutations in PKD2. Identification of these mutations is central to identifying functionally important regions of gene and to understanding the mechanisms underlying the pathogenesis of the disorder. The current study describes mutations in six type 2 ADPKD families. Two single base substitution mutations discovered in the ORF in exon 14 constitute the most COOH-terminal pathogenic variants described to date. One of these mutations is a nonsense change and the other encodes an apparent missense variant. Reverse transcription-PCR from patient lymphoblast RNA showed that, in addition, both mutations resulted in out-of-frame splice variants by activating cryptic splice sites via different mechanisms. The apparent missense variant produced such a strong splicing signal that the processed transcript from the mutant chromosome did not contain any of the normally spliced, missense product. A third mutation, a nonconservative missense change effecting a negatively charged residue in the third transmembrane span, is likely pathogenic and defines a highly conserved residue consistent with a potential channel subunit function for polycystin-2. The remaining three mutations included two frame shifts resulting from deletion of one or two bases in exons 6 and 10, respectively, and a nonsense mutation due to a single base substitution in exon 4. The study also defined a novel intragenic polymorphism in exon 1 that will be useful in analyzing "second hits" in PKD2. Finally, the study demonstrates that there are reduced levels of normal polycystin-2 protein in lymphoblast lines from PKD2-affected individuals and that truncated mutant polycystin-2 cannot be detected in patient lymphoblasts, suggesting that the latter may be unstable in at least some tissues. The mutations described will serve as critical reagents for future functional studies in PKD2.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients.
- Authors: Torra R, Badenas C, Pérez-Oller L, Luis J, Millán S, Nicolau C, Oppenheimer F, Milà M, Darnell A
- Issue date: 2000 Oct
- Defective pre-mRNA splicing in PKD1 due to presumed missense and synonymous mutations causing autosomal dominant polycystic disease.
- Authors: Gonzalez-Paredes FJ, Ramos-Trujillo E, Claverie-Martin F
- Issue date: 2014 Aug 10
- [Mutational analysis of the PKD1 and PKD2 (type 1 and 2 dominant autosomal polycystic kidney) genes].
- Authors: Torra R, Badenas C, Pérez-Oller L, San Millán JL, Tellería D, Estivill X, Darnell A
- Issue date: 2000 Jan-Feb
- PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease.
- Authors: Vouk K, Strmecki L, Stekrova J, Reiterova J, Bidovec M, Hudler P, Kenig A, Jereb S, Zupanic-Pajnic I, Balazic J, Haarpaintner G, Leskovar B, Adamlje A, Skoflic A, Dovc R, Hojs R, Komel R
- Issue date: 2006 Jan 23
- Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease.
- Authors: Torra R, Viribay M, Tellería D, Badenas C, Watson M, Harris P, Darnell A, San Millán JL
- Issue date: 1999 Jul