Mutational analysis within the 3' region of the PKD1 gene
- PMID: 10200984
- DOI: 10.1046/j.1523-1755.1999.00368.x
Mutational analysis within the 3' region of the PKD1 gene
Abstract
Background: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases in humans, affecting 1 out of 1000 individuals. At least three different genes are involved in this disease. The search for mutations in PKD1 is complicated because most of the transcript is encoded by a genomic region reiterated more proximally on chromosome 16, and no prevalent mutation has been reported.
Methods: We have screened DNA from exon 43 through exon 46 and intron 40 of the PKD1 sequence by single-stranded conformational polymorphism (SSCP) analysis in 175 ADPKD patients.
Results: We have found 25 differences with respect to the reported PKD1 DNA sequence, seven of which are mutations (Q4041X, Q4124X, IVS44-1G-->C, IVS45-1G-->A, 12801del28, R4275W, and Q4224P). We found different phenotypical expressions of the same mutation in the families studied. We have detected several common polymorphisms, and some of them cosegregate, suggesting a common origin of these alleles in PKD1.
Conclusions: The detection of only seven mutations in 175 unrelated ADPKD patients for this region of the PKD1 analyzed suggests that mutations could be widespread throughout all of the gene and that a prevalent mutation is not expected to occur. The identified PKD1 missense mutations may help to refine critical regions of the protein. Until a quicker and more sensitive method for the detection of mutations becomes available, linkage studies will continue to be the basis for the molecular diagnosis of ADPKD families.
Similar articles
-
[Mutational analysis of the PKD1 and PKD2 (type 1 and 2 dominant autosomal polycystic kidney) genes].Nefrologia. 2000 Jan-Feb;20(1):39-46. Nefrologia. 2000. PMID: 10822721 Spanish.
-
Novel mutations in the duplicated region of the polycystic kidney disease 1 (PKD1) gene provides supporting evidence for gene conversion.Genet Test. 2000;4(4):365-70. doi: 10.1089/109065700750065108. Genet Test. 2000. PMID: 11216660
-
Mutation detection in the duplicated region of the polycystic kidney disease 1 (PKD1) gene in PKD1-linked Australian families.Hum Mutat. 2002 Mar;19(3):240-50. doi: 10.1002/humu.10045. Hum Mutat. 2002. PMID: 11857740
-
Polycystic kidney disease. 1: Identification and analysis of the primary defect.J Am Soc Nephrol. 1995 Oct;6(4):1125-33. doi: 10.1681/ASN.V641125. J Am Soc Nephrol. 1995. PMID: 8589278 Review.
-
Autosomal dominant polycystic kidney disease: molecular analysis.Hum Mol Genet. 1995;4 Spec No:1745-9. doi: 10.1093/hmg/4.suppl_1.1745. Hum Mol Genet. 1995. PMID: 8541874 Review.
Cited by
-
Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.PLoS One. 2012;7(6):e36798. doi: 10.1371/journal.pone.0036798. Epub 2012 Jun 4. PLoS One. 2012. PMID: 22675472 Free PMC article.
-
Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation.J Inherit Metab Dis. 2006 Aug;29(4):580-5. doi: 10.1007/s10545-006-0344-6. J Inherit Metab Dis. 2006. PMID: 16817012
-
High Resolution Melt analysis for mutation screening in PKD1 and PKD2.BMC Nephrol. 2011 Oct 18;12:57. doi: 10.1186/1471-2369-12-57. BMC Nephrol. 2011. PMID: 22008521 Free PMC article.
-
Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex.Hum Mol Genet. 2014 May 15;23(10):2769-79. doi: 10.1093/hmg/ddt672. Epub 2014 Jan 2. Hum Mol Genet. 2014. PMID: 24385601 Free PMC article.
-
Regulation of polycystin-1 ciliary trafficking by motifs at its C-terminus and polycystin-2 but not by cleavage at the GPS site.J Cell Sci. 2015 Nov 15;128(22):4063-73. doi: 10.1242/jcs.160556. Epub 2015 Oct 1. J Cell Sci. 2015. PMID: 26430213 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
