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KMID : 0366220130480030206
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Korean Journal of Hematology
2013 Volume.48 No. 3 p.206 ~ p.210
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Sequence variation data of F8 and F9 genes in functionally validated control individuals: implications on the molecular diagnosis of hemophilia
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Seo Ja-Young
Jang Mi-Ae
Kim Hee-Jung
Kim Sun-Hee
Kim Hee-Jin
Lee Ki-O
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Abstract
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Background: The F8 and F9 genes encode for coagulation factor VIII (FVIII) and FIX, respectively, and mutations in these genes are the genetic basis of hemophilia A/B. To determine whether a sequence variation in F8/F9 is a disease-causing mutation, frequency data from a control population is needed. This study aimed to obtain data on sequence variation in F8/F9 in a set of functionally validated control chromosomes of Korean descent.
Methods: We re-sequenced F8 and F9 from DNA samples of 100 Korean male control individuals with normal PT, aPTT, and FVIII activity. PCR and direct sequencing analyses were per-formed using primer pairs to cover all coding regions and the flanking intronic sequences.
Results: Thirteen individuals (13%) were hemizygous for sequence variations in the coding region of F8. Six (6%) had c.3780C＞G (p.Asp1260Glu), five (5%) had c.3864A＞C (p.Ser1288=). One each individual (1%) had c.4794G＞T (p.Glu1598Asp) and c.5069A＞G (p.Glu1690Gly). Asp1260Glu and Ser1288= were known SNPs (rs1800291 and rs1800292, respectively). Glu1598Asp was assigned as a missense mutation in public databases (HGMD and HAMSTeRS), and Glu1690Gly was a novel variation. Based on the normal FVIII activities in control individuals carrying these variations (109% and 148%, respectively), they were considered to be rare SNPs. No variation was observed in F9 of control individuals.
Conclusion: A significant proportion of control individuals carried sequence variations in F8, but not in F9. These results can be used as a reference dataset for molecular diagnosis of hemo-philia A and B, particularly in Korea.
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KEYWORD
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Hemophilia, F8, F9, Sequence variation, Control population, Korea
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