Frameshift mutations with severe and moderate clinical phenotypes in Thai hemophilia A patients

Hum Mutat. 2000 Dec;16(6):530-1. doi: 10.1002/1098-1004(200012)16:6<530::AID-HUMU16>3.0.CO;2-3.


Six frameshift mutations in exon 14 of the factor VIII gene were identified in Thai hemophilia A patients. Although all these mutations created premature stop codons and expected to cause severe disease, the molecular defects and clinical severity were in discrepancy in some patients. Four mutations (delT3490, delACAC3618-21, delGA4429-30, and delA4658) were found in the patients with the severe clinical phenotype while two (delA3629-37 and insA4372-9) were observed in the patients who had moderate severity, with FVIII:C of 4.2 and 2.8%. The frameshift mutations in these two patients were due to deletion and insertion of an 'A' nucleotide in the stretches of 9As and 8As in codons 1191-4 and 1439-41, respectively. This indicates that deletion or insertion in the stretches of poly A nucleotides in exon 14 of the factor VIII gene is a likely cause of the moderate clinical severity in some cases of Thai hemophilia A patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Inversion
  • Factor VIII / genetics
  • Factor VIII / physiology
  • Frameshift Mutation / genetics*
  • Hemophilia A / genetics*
  • Humans
  • Male
  • Nuclear Family
  • Phenotype
  • Sequence Deletion / genetics
  • Thailand


  • Factor VIII