title: Frameshift mutations with severe and moderate clinical phenotypes in Thai hemophilia A patients.
abstract: 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.
authors: Institute of Molecular Biology and Genetics, Mahidol University, Salaya Campus, Nakhon Pathom, Mahidol University, Bangkok, Thailand.
authors: V
authors: V
authors: Akkarapatumwong
authors: S
authors: S
authors: Intorasoot
authors: S
authors: S
authors: Oranwiroon
authors: P
authors: P
authors: Thano-Otarakul
authors: P
authors: P
authors: Pung-Amritt
authors: G
authors: G
authors: Veerakul
authors: C
authors: C
authors: Mahasandana
authors: S
authors: S
authors: Panyim
authors: P
authors: P
authors: Yenchitsomanus
mesh_terms: D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics / Q000502:physiology; D016368:Frameshift Mutation / Q000235:genetics*; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008297:Male; D009679:Nuclear Family; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics; D013785:Thailand
chemical_list: D005169:Factor VIII