title: Identification of seven novel mutations in the factor VIII gene in 18 unrelated Chinese patients with hemophilia A.
abstract: BACKGROUND
  Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by decreased activity of factor VIII (FVIII) due to heterogenous mutations in the FVIII coding gene (F8). The type of mutation plays an important role in the FVIII inhibitor formation. To date, several studies on the spectra of F8 defects have been performed in Western populations, but similar studies in Asian races are scarce. Here, we reported the distribution of the F8 gene mutations in 18 unrelated Chinese patients with HA.
  
  
  METHODS
  Intron 22 and intron 1 inversions in the F8 gene were screened in 158 unrelated patients with HA using a long-distance PCR and multiplex PCR method. Direct sequencing of the coding region of the F8 gene was used to identify the mutations responsible for HA in 18 unrelated Chinese HA patients who were negative for intron 22 and intron 1 inversions; sequences were compared with the HAMSTeRS database. A clotting method was used to assay the FVIII activity level and the Bethesda assay was used to detect the FVIII inhibitor.
  
  
  RESULTS
  A total of 18 different HA F8 mutations were identified, seven of which were described for the first time. These novel mutations included five small deletions, one point mutation and one small insertion. One novel mutation (4382-3 AC deletion) was associated with inhibitor development.
  
  
  CONCLUSIONS
  These data extend our insight into the mechanisms by which novel amino acid mutations may lead to HA and how the HA patient genotypes influence the risk of FVIII inhibitor.
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China.
authors.forename: Bao-lai
authors.initials: BL
authors.lastname: Hua
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.forename: Lian-kai
authors.initials: LK
authors.lastname: Fan
authors.forename: Kui-xing
authors.initials: KX
authors.lastname: Li
authors.forename: Bai
authors.initials: B
authors.lastname: Xiao
authors.forename: Jing-zhong
authors.initials: JZ
authors.lastname: Liu
authors.forename: Yong-qiang
authors.initials: YQ
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D005169:Factor VIII