Document Detail

Novel splicing and missense mutations in autosomal dominant polycystic kidney disease 1 (PKD1) gene: expression of mutated genes.
MedLine Citation:
PMID:  11058904     Owner:  NLM     Status:  MEDLINE    
Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder mostly characterized by cyst formation in kidney tubules. The majority of ADPKD cases is caused by mutations in the PKD1 gene, but no prevalent mutation has been reported. By heteroduplex analysis of the 3' single-copy region of the gene, we have searched for mutations in subjects from 40 ADPKD families of Northern Italy. Seven novel polymorphisms and three novel disease-associated mutations (R3718Q, L3851P and IVS45+56del25) were identified. Both missense mutations are located in the major extracellular loop of polycystin-1. The 25 bp deletion inside intron 45 did not affect 5' and 3' consensus splicing sites, but caused a 56 nucleotide out of frame-deletion due to activation of a cryptic 3' splice site in exon 46. The mutated RNA should produce a truncated polycystin 1 at the G binding peptide in the intracellular C-terminal end of the protein. RT-PCR analysis showed that the disease-associated mutations were present in transcribed sequences. In particular, RNA analysis of BHK cells transfected with PKD1 genomic DNA, including the deleted intron, showed that no normal transcript is produced by the deleted gene. This intronic mutation, found in a large pedigree, seems to be associated with a prevalence of cerebrovascular disease.
G Aguiari; S Savelli; M Garbo; A Bozza; G Augello; L Penolazzi; E De Paoli Vitali; C La Torre; G Cappelli; R Piva; L del Senno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human mutation     Volume:  16     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-06     Completed Date:  2000-11-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  444-5     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi, Ferrara, Italy.
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MeSH Terms
Alternative Splicing / genetics*
Base Sequence / genetics
Gene Expression / genetics*
Kidney Failure, Chronic / genetics
Middle Aged
Molecular Sequence Data
Mutation, Missense / genetics*
Polycystic Kidney, Autosomal Dominant / genetics*
Polymorphism, Genetic
Protein Biosynthesis*
Protein Isoforms / genetics
Proteins / genetics*
TRPP Cation Channels
Reg. No./Substance:
0/Protein Isoforms; 0/Proteins; 0/TRPP Cation Channels; 0/polycystic kidney disease 1 protein

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