Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene
- Univ. of Geneva (Switzerland)
- Tokyo Medical College (Japan); and others
Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A{sub 8}TA{sub 2} sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient`s plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) {open_quotes}ribosomal frameshifting{close_quotes} resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A{sub 10} instead of A{sub 8}TA{sub 2}, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. 36 refs., 6 figs.
- OSTI ID:
- 518540
- Journal Information:
- American Journal of Human Genetics, Vol. 60, Issue 3; Other Information: PBD: Mar 1997
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
PATIENTS
HEMIC DISEASES
PHENOTYPE
HUMAN X CHROMOSOME
GENETIC MAPPING
BLOOD COAGULATION FACTORS
DNA-CLONING
GENE REGULATION
GENE MUTATIONS
DNA SEQUENCING
TRANSCRIPTION
STRUCTURE-ACTIVITY RELATIONSHIPS
HEMOPHILIA
NUCLEOTIDES
EXONS
ADENOSINE
DNA REPLICATION
POLYPEPTIDES
JAPAN
ELECTROPHORESIS