PMID- 10364515
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 1
DP  - 1999 Jul
TI  - Identification of mutations in the repeated part of the autosomal dominant
      polycystic kidney disease type 1 gene, PKD1, by long-range PCR.
PG  - 39-49
AB  - We have used long-range PCR to identify mutations in the duplicated part of the
      PKD1 gene. By means of a PKD1-specific primer in intron 1, an approximately
      13.6-kb PCR product that includes exons 2-15 of the PKD1 gene has been used to
      search for mutations, by direct sequence analysis. This region contains the
      majority of the predicted extracellular domains of the PKD1-gene product,
      polycystin, including the 16 novel PKD domains that have similarity to
      immunoglobulin-like domains found in many cell-adhesion molecules and
      cell-surface receptors. Direct sequence analysis of exons encoding all the 16 PKD
      domains was performed on PCR products from a group of 24 unrelated patients with 
      autosomal dominant polycystic kidney disease (ADPKD [MIM 173900]). Seven novel
      mutations were found in a screening of 42% of the PKD1-coding region in each
      patient, representing a 29% detection rate; these mutations included two
      deletions (one of 3 kb and the other of 28 bp), one single-base insertion, and
      four nucleotide substitutions (one splice site, one nonsense, and two missense). 
      Five of these mutations would be predicted to cause a prematurely truncated
      protein. Two coding and 18 silent polymorphisms were also found. When, for the
      PKD1 gene, this method is coupled with existing mutation-detection methods,
      virtually the whole of this large, complex gene can now be screened for
      mutations.
FAU - Thomas, R
AU  - Thomas R
AD  - Departments of Medical Genetics, Addenbrooke's Hospital, Cambridge, United
      Kingdom.
FAU - McConnell, R
AU  - McConnell R
FAU - Whittacker, J
AU  - Whittacker J
FAU - Kirkpatrick, P
AU  - Kirkpatrick P
FAU - Bradley, J
AU  - Bradley J
FAU - Sandford, R
AU  - Sandford R
LA  - eng
SI  - GENBANK/AC002039
SI  - GENBANK/L33234
SI  - GENBANK/L39891
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Proteins)
RN  - 0 (TRPP Cation Channels)
RN  - 0 (polycystic kidney disease 1 protein)
SB  - IM
MH  - Base Sequence
MH  - Exons
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Polycystic Kidney, Autosomal Dominant/genetics
MH  - Polymerase Chain Reaction/*methods
MH  - Polymorphism, Genetic
MH  - Protein Structure, Secondary
MH  - Proteins/chemistry/*genetics
MH  - Sequence Analysis, DNA/methods
MH  - TRPP Cation Channels
PMC - PMC1378073
EDAT- 1999/06/12 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/06/12 10:00
PHST- 1999/06/12 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/06/12 10:00 [entrez]
AID - S0002-9297(07)63726-4 [pii]
AID - 10.1086/302460 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Jul;65(1):39-49. doi: 10.1086/302460.