PMID- 10411676
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20071018
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 1
DP  - 1999 Jul
TI  - Seven novel mutations of the PKD2 gene in families with autosomal dominant
      polycystic kidney disease.
PG  - 28-33
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically
      heterogeneous, with at least three chromosomal loci accounting for the disease.
      Mutations in the PKD2 gene on the long arm of chromosome 4 are expected to be
      responsible for approximately 15% of cases of ADPKD. METHODS: We report a
      systematic screening for mutations covering the 15 exons of the PKD2 gene in
      eight unrelated families with ADPKD type 2, using the heteroduplex technique.
      RESULTS: Seven novel mutations were identified and characterized that, together
      with the previously described changes, amount to a detection rate of 85% in the
      population studied. The newly described mutations are two nonsense mutations, a 1
      bp deletion, a 1 bp insertion, a mutation that involves both a substitution and a
      deletion (2511AG-->C), a complex mutation in exon 6 consisting of a simultaneous 
      7 bp inversion and a 4 bp deletion, and the last one is a G-->C transversion that
      may be a missense mutation. Most of these mutations are expected to lead to the
      formation of shorter truncated proteins lacking the carboxyl terminus of PKD2. We
      have also characterized a frequent polymorphism, Arg-Pro, at codon 28 in this
      gene. The clinical features of these PKD2 patients are similar to the previously 
      described, with the mean age of end-stage renal disease being 75.5 years (SE +/- 
      3.8 years). CONCLUSIONS: Our results confirm that many different mutations are
      likely to be responsible for the disease and that most pathogenic defects
      probably are point or small changes in the coding region of the gene.
FAU - Torra, R
AU  - Torra R
AD  - Servicio de Nefrologia, Hospital Clinic, Institut d'Investigacions Biomediques
      August Pi i Sunyer, Universidad de Barcelona, Spain. rtorra@medicina.ub.es
FAU - Viribay, M
AU  - Viribay M
FAU - Telleria, D
AU  - Telleria D
FAU - Badenas, C
AU  - Badenas C
FAU - Watson, M
AU  - Watson M
FAU - Harris, P
AU  - Harris P
FAU - Darnell, A
AU  - Darnell A
FAU - San Millan, J L
AU  - San Millan JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Membrane Proteins)
RN  - 0 (TRPP Cation Channels)
RN  - 0 (polycystic kidney disease 2 protein)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Base Sequence/genetics
MH  - Exons/genetics
MH  - Frameshift Mutation/genetics
MH  - Humans
MH  - Membrane Proteins/*genetics
MH  - Mutation/*genetics
MH  - Mutation, Missense/genetics
MH  - Polycystic Kidney, Autosomal Dominant/*genetics
MH  - Polymorphism, Genetic/genetics
MH  - Survival Analysis
MH  - TRPP Cation Channels
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - S0085-2538(15)46259-3 [pii]
AID - 10.1046/j.1523-1755.1999.00534.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Jul;56(1):28-33. doi: 10.1046/j.1523-1755.1999.00534.x.