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Mutations of the factor VIII gene in Thai hemophilia A patients
Author(s) -
Akkarapatumwong V.,
Oranwiroon S.,
Pungamritt P.,
Treesucon A.,
Thanootarakul P.,
Veerakul G.,
Mahasandana C.,
Panyim S.,
Yenchitsomanus P.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200001)15:1<117::aid-humu27>3.0.co;2-e
Subject(s) - missense mutation , genetics , nonsense mutation , biology , gene , single strand conformation polymorphism , exon , microbiology and biotechnology , mutation , coding region , polymerase chain reaction , factor ix , silent mutation , genomic dna , factor v , gene mutation , medicine , thrombosis
Hemophilia A is a common X‐linked bleeding disorder caused by mutations in the coagulation factor VIII gene. The entire coding and essential sequences of the factor VIII gene were generated by a combination of genomic DNA amplification and long reverse transcription‐polymerase chain reaction (long RT‐PCR) using factor VIII transcripts prepared from lymphocytes. Mutations were then screened by non‐radioactive single strand conformation polymorphism (SSCP) analysis and characterized by DNA sequencing. We have identified six potentially pathogenic mutations in the factor VIII gene in Thai hemophilia A patients, including two nonsense mutations (R‐5X and R1966X), three missense mutations (D542Y, G1850V, and G2325C), and a 4‐bp insertion (ACTA) at codon 2245. Three of these mutations (D542Y, G2325C, and 4‐bp insertion) have never been previously reported, and the ins2245 is the first example of such insertion probably causing factor VIII elongation. R1966X, D542Y, G1850V, and 4‐bp insertion were associated with a severe hemophiliac phenotype whereas R‐5X and G2325C were observed in moderately affected patients. Mutations in the factor VIII gene in Thai hemophilia A patients are likely to be heterogeneous. This study represents the first attempt to further the understanding of the molecular basis of hemophilia A in Thai. Hum Mutat 15:177–118, 2000. © 2000 Wiley‐Liss, Inc.