PMID- 10577909
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 6
DP  - 1999 Dec
TI  - Mutation detection of PKD1 identifies a novel mutation common to three families
      with aneurysms and/or very-early-onset disease.
PG  - 1561-71
AB  - It is known that several of the most severe complications of autosomal-dominant
      polycystic kidney disease, such as intracranial aneurysms, cluster in families.
      There have been no studies reported to date, however, that have attempted to
      correlate severely affected pedigrees with a particular genotype. Until recently,
      in fact, mutation detection for most of the PKD1 gene was virtually impossible
      because of the presence of several highly homologous loci also located on
      chromosome 16. In this report we describe a cluster of 4 bp in exon 15 that are
      unique to PKD1. Forward and reverse PKD1-specific primers were designed in this
      location to amplify regions of the gene from exons 11-21 by use of long-range
      PCR. The two templates described were used to analyze 35 pedigrees selected for
      study because they included individuals with either intracranial aneurysms and/or
      very-early-onset disease. We identified eight novel truncating mutations, two
      missense mutations not found in a panel of controls, and several informative
      polymorphisms. Many of the polymorphisms were also present in the homologous
      loci, supporting the idea that they may serve as a reservoir for genetic
      variability in the PKD1 gene. Surprisingly, we found that three independently
      ascertained pedigrees had an identical 2-bp deletion in exon 15. This raises the 
      possibility that particular genotypes may be associated with more-severe disease.
FAU - Watnick, T
AU  - Watnick T
AD  - 1Johns Hopkins University School of Medicine, Division of Nephrology, Baltimore, 
      MD 21205, USA.
FAU - Phakdeekitcharoen, B
AU  - Phakdeekitcharoen B
FAU - Johnson, A
AU  - Johnson A
FAU - Gandolph, M
AU  - Gandolph M
FAU - Wang, M
AU  - Wang M
FAU - Briefel, G
AU  - Briefel G
FAU - Klinger, K W
AU  - Klinger KW
FAU - Kimberling, W
AU  - Kimberling W
FAU - Gabow, P
AU  - Gabow P
FAU - Germino, G G
AU  - Germino GG
LA  - eng
GR  - DK48006/DK/NIDDK NIH HHS/United States
GR  - R37 DK048006/DK/NIDDK NIH HHS/United States
GR  - F05 TW005393/TW/FIC NIH HHS/United States
GR  - P01 DK034039/DK/NIDDK NIH HHS/United States
GR  - DK4853/DK/NIDDK NIH HHS/United States
GR  - TW05393/TW/FIC NIH HHS/United States
GR  - R01 DK048006/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
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  - Adult
MH  - Age of Onset
MH  - Base Sequence
MH  - Exons/genetics
MH  - Female
MH  - Genetic Variation/genetics
MH  - Genotype
MH  - Humans
MH  - Intracranial Aneurysm/*epidemiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - Polycystic Kidney, Autosomal Dominant/*genetics
MH  - Polymerase Chain Reaction/methods
MH  - Polymorphism, Genetic/genetics
MH  - Protein Structure, Secondary
MH  - Proteins/chemistry/*genetics
MH  - TRPP Cation Channels
MH  - Templates, Genetic
PMC - PMC1288366
EDAT- 1999/12/01 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/12/01 09:00
PHST- 1999/12/01 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/12/01 09:00 [entrez]
AID - S0002-9297(07)63575-7 [pii]
AID - 10.1086/302657 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Dec;65(6):1561-71. doi: 10.1086/302657.