Abstract
The PKD1-gene encodes a 14 kb transcript spanning a 50 kb genomic interval. Two-thirds of the gene is reiterated at another locus on the same chromosome. Using Long Range PCR with primers in intron 1 and exon 11, 6.8 kb PKD1 specific fragments were generated on genomic DNA. These products were used as templates for nested PCR's to screen exons 2–10 by Denaturing Gradient Gel Electrophoresis (DGGE). Upon analysis of 36 patients, a total of 11 different sequence variants were observed: A nonsense mutation in exon 2, a frameshift mutation in exon 8 and furthermore, two amino acid changes, two silent polymorphisms and five intronic variants.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Peters DJM, Sandkuijl LA . Genetic heterogeneity of polycystic kidney disease in Europe in Breuning MH, Devoto M, Romeo G, (eds) Contributions to Nephrology Vol. 97: Polycystic Kidney Disease Basel: Karger 1992 pp128–139
Hateboer N, Dijk MA, Coto E et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group Lancet 1999 353: 103–107
The European Polycystic Kidney Disease Consortium: Ward C, Peral B, Hughes J, Thomas S, Gamble V, MacCarthy A et al. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16 Cell 1994 77: 881–894
Rossetti S, Strmecki L, Gamble V et al. Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications Am J Hum Genet 2001 68: 46–63
Watnick TJ, Piontek KB, Cordal TM et al. An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection Hum Mol Genet 1997 6: 1473–1481
Peral B, Gamble V, Strong C et al. Identification of mutations in the duplicated region of the polycystic kidney disease 1 (PKD1) gene by a novel approach Am J Hum Genet 1997 61: 1399–1410
Thomas R, McConnell R, Whittacker J, Kirkpatrick P, Bradley J, Sandford R . Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR Am J Hum Genet 1999 65: 39–49
Sheffield VC, Cox DR, Lerman LS, Meyers RM . Attachment of a 40-base-pair G+C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes Proc Natl Acad Sci USA 1989 86: 232–236
Phakdeekitcharoen B, Watnick TJ, Germino GG . Mutation analysis of the entire replicated portion of pkd1 using genomic dna samples J Am Soc Nephrol 2001 12: 955–963
Perrichot RA, Mercier B, Simon PM, Whebe B, Cledes J, Ferec C . DGGE screening of PKD1 gene reveals novel mutations in a large cohort of 146 unrelated patients Hum Genet 1999 105: 231–239
Perrichot R, Mercier B, Quere I et al. Novel mutations in the duplicated region of PKD1 gene Eur J Hum Genet 2000 8: 353–359
Veldhuisen B, Saris JJ, de Haij S et al. A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2) Am J Hum Genet 1997 61: 547–555
Antonarakis SE . Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group Hum Mutat 1998 11: 1–3
Acknowledgements
This research was supported by a grant from the Dutch Kidney Foundation (C95-1511). The authors thank patients and clinicians for participation in the study, MP Villerius from the Leiden Genome Technology Center for sequencing, L Spruit for technical assistance and S White for critical reading of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Peters, D., Ariyurek, Y., van Dijk, M. et al. Mutation detection for exons 2 to 10 of the Polycystic Kidney Disease 1 (PKD1)-gene by DGGE. Eur J Hum Genet 9, 957–960 (2001). https://doi.org/10.1038/sj.ejhg.5200756
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5200756
Keywords
This article is cited by
-
“Unnatural resources?”: parallels and distinctions between the Newfoundland Genome and traditional resource sectors
Journal of Community Genetics (2024)
-
System analysis of gene mutations and clinical phenotype in Chinese patients with autosomal-dominant polycystic kidney disease
Scientific Reports (2016)
-
Novel PKD1 and PKD2 mutations in Taiwanese patients with autosomal dominant polycystic kidney disease
Journal of Human Genetics (2013)
-
Novel and de novo PKD1 mutations identified by multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP)
BMC Medical Genetics (2004)
