title: [Frequency of intron 1 inversion of factor VIII gene in Chinese hemophilia A patients with case report of a female patient with heterozygous intron 1 inversion].
abstract: OBJECTIVE
  To investigate the frequency of intron 1 inversion (inv1) in FVIII gene in Chinese hemophilia A (HA) patients and to investigate the mechanism of pathogenesis.
  
  
  METHODS
  Peripheral blood samples were collected from 158 unrelated HA patients, aged 20 (1 - 73), including one female HA patient, aged 5, and several family members of a patient positive in inv1. One-stage method was used to assay the FVIII activity (FVIII:C). Long distance PCR and multiple PCR in duplex reactions were used to screen for the intron 22 inversion (inv22) and inv1 of the FVIII coding gene (F8). The F8 coding sequence was amplified with PCR and sequenced with an automatic sequencer.
  
  
  RESULTS
  Two unrelated patients (pedigrees) were detected as inv1 positive with a positive rate of 1.26%. A rare female HA patient with inv1 was also discovered in a positive family (3 HA cases were found in this family and regarded as one case in calculating the total detection rate). The full length of FVIII was sequenced, and no other mutation was detected.
  
  
  CONCLUSIONS
  There frequency of FVIII inv1 is low in Chinese HA patients compared with other populations. Female HA patients are heterozygous for FVIII inv1 and that may be resulted from nonrandom inactivation of X chromosome.
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China.
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: Bai
authors.initials: B
authors.lastname: Xiao
authors.forename: Bao-lai
authors.initials: BL
authors.lastname: Hua
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; D007446:Chromosome Inversion / Q000235:genetics*; D041321:Chromosomes, Human, X; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007438:Introns; D008875:Middle Aged
chemical_list: D005169:Factor VIII