[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].
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.
Yan
Zhen-yu
ZY
Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China.
Liang
Yan
Y
Yan
Mei
M
Fan
Lian-kai
LK
Xiao
Bai
B
Hua
Bao-lai
BL
Liu
Jing-zhong
JZ
Zhao
Yong-qiang
YQ
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
D005169:Factor VIII