Official websites use .gov
A
.gov
website belongs to an official government organization in the
United States.
Secure .gov websites use HTTPS
A
lock
(
) or
https://
means you’ve safely connected to the .gov website. Share sensitive
information only on official, secure websites.
PubMed ID:
18818683
Public Release Type:
Journal
Publication Year: 2008
Affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
DOI:
https://doi.org/10.1038/ki.2008.485
Authors:
Consugar MB,
Wong WC,
Lundquist PA,
Rossetti S,
Kubly VJ,
Walker DL,
Rangel LJ,
Aspinwall R,
Niaudet WP,
Ozen S,
David A,
Velinov M,
Bergstralh EJ,
Bae KT,
Chapman AB,
Guay-Woodford LM,
Grantham JJ,
Torres VE,
Sampson JR,
Dawson BD,
Harris PC,
CRISP Consortium,
Bennett WM,
Meyers CM,
Moen LK,
Miller JP,
Bost JE,
King BF,
Wetzel LH,
Baumgarten DA,
Kenney PJ,
Mahan J,
Stafford B,
Stevens L,
Cornwell K,
Watkins D,
Langley S,
Trull P
Studies:
Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease
Large DNA rearrangements account for about 8% of disease mutations and are more common in duplicated genomic regions, where they are difficult to detect. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. PKD1 is located in an intrachromosomally duplicated region. A tuberous sclerosis gene, TSC2, lies immediately adjacent to PKD1 and large deletions can result in the PKD1/TSC2 contiguous gene deletion syndrome. To rapidly identify large rearrangements, a multiplex ligation-dependent probe amplification assay was developed employing base-pair differences between PKD1 and the six pseudogenes to generate PKD1-specific probes. All changes in a set of 25 previously defined deletions in PKD1, PKD2 and PKD1/TSC2 were detected by this assay and we also found 14 new mutations at these loci. About 4% of the ADPKD patients in the CRISP study were found to have gross rearrangements, and these accounted for about a third of base-pair mutation negative families. Sensitivity of the assay showed that about 40% of PKD1/TSC contiguous gene deletion syndrome families contained mosaic cases. Characterization of a family found to be mosaic for a PKD1 deletion is discussed here to illustrate family risk and donor selection considerations. Our assay improves detection levels and the reliability of molecular testing of patients with ADPKD.
