| Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A. | |
MedLine Citation:
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PMID: 1301932 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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C Diamond; S Kogan; B Levinson; J Gitschier |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Human mutation Volume: 1 ISSN: 1059-7794 ISO Abbreviation: Hum. Mutat. Publication Date: 1992 |
Date Detail:
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Created Date: 1993-06-10 Completed Date: 1993-06-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9215429 Medline TA: Hum Mutat Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 248-57 Citation Subset: IM |
Affiliation:
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Howard Hughes Medical Institute, University of California, San Francisco 94143. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/M13699; M14335; M38337 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HL42968/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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