Document Detail


Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.
MedLine Citation:
PMID:  1301932     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations leading to hemophilia A by substitution of amino acids in coagulation factor VIII may provide important clues to the structure and function of this large and enigmatic protein. To efficiently find missense mutations, hemophiliacs with mild and moderately severe forms of the disease were surveyed. DNA samples from affected individuals were assayed for mutations by denaturing gradient gel electrophoresis following DNA amplification of target regions, which included all coding regions except for that of the dispensable B domain. Missense mutations were observed in 20 of the 34 patients examined, with identical mutations found in five pairs of patients. All mutations were found in the repetitive A and C domains. By aligning these domains in factor VIII with homologous domains in factor V, ceruloplasmin, and the mouse milk fat globule membrane protein, it was determined that most mutations change amino acids in areas of strong sequence conservation. Three additional mutations were detected, including a point mutation in an intron, a stop codon mutation, and a silent base change. Ten of the 18 different mutations discovered in this patient population are reported here for the first time.
Authors:
C Diamond; S Kogan; B Levinson; J Gitschier
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human mutation     Volume:  1     ISSN:  1059-7794     ISO Abbreviation:  Hum. Mutat.     Publication Date:  1992  
Date Detail:
Created Date:  1993-06-10     Completed Date:  1993-06-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  248-57     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/M13699;  M14335;  M38337
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Base Sequence
Conserved Sequence
DNA / genetics
DNA Mutational Analysis
DNA Probes
Factor VIII / genetics*
Hemophilia A / genetics*
Humans
Male
Molecular Sequence Data
Phenotype
Grant Support
ID/Acronym/Agency:
HL42968/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Probes; 9001-27-8/Factor VIII; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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