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

✍ Scribed by Varaporn Akkarapatumwong; Sorasak Intorasoot; Sumalee Oranwiroon; Prapaporn Thano-otarakul; Parichat Pung-amritt; Gavivann Veerakul; Chularatana Mahasandana; Sakol Panyim; Pa-thai Yenchitsomanus

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 17 KB
• Volume: 16
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/1098-1004(200012)16:6<530::aid-humu16>3.0.co;2-3

✦ Synopsis

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.