Analysis of mutations in the entire coding sequence of the factor VIII gene

Journal Article · Thu Sep 01 00:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134166

Bidichadani, S I; Lanyon, W G; Connor, J M ^[1]

---

1. Glascow Univ. (United Kingdom); and others

Hemophilia A is a common X-linked recessive disorder of bleeding caused by deleterious mutations in the gene for clotting factor VIII. The large size of the factor VIII gene, the high frequency of de novo mutations and its tissue-specific expression complicate the detection of mutations. We have used a combination of RT-PCR of ectopic factor VIII transcripts and genomic DNA-PCRs to amplify the entire essential sequence of the factor VIII gene. This is followed by chemical mismatch cleavage analysis and direct sequencing in order to facilitate a comprehensive search for mutations. We describe the characterization of nine potentially pathogenic mutations, six of which are novel. In each case, a correlation of the genotype with the observed phenotype is presented. In order to evaluate the pathogenicity of the five missense mutations detected, we have analyzed them for evolutionary sequence conservation and for their involvement of sequence motifs catalogued in the PROSITE database of protein sites and patterns.

• OSTI ID: 134166
• Report Number(s): CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0902
• Journal Information: American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
HEMOPHILIA
GENES
PATIENTS
HEREDITARY DISEASES
PHENOTYPE
GENE MUTATIONS
MUTATION FREQUENCY
TRANSCRIPTION
DNA SEQUENCING
BIOLOGICAL EVOLUTION
DETECTION
GENOTYPE
CORRELATIONS
BLOOD COAGULATION FACTORS
HUMAN X CHROMOSOME
RECESSIVE MUTATIONS
GENE REGULATION
POLYMERASE CHAIN REACTION
PROTEINS