title: Genetic diagnosis in Hemophilia A from southern China: five novel mutations and one preimplantation genetic analysis.
abstract: BACKGROUND
  As there is currently no complete cure for hemophilia A (HA), the identification of pathogenic mutations in factor VIII (FVIII) gene from HA patients and carriers, which can contribute to genetic counseling prenatal diagnosis, and preimplantation genetic diagnosis (PGD), is an important step to prevent HA.
  
  
  METHODS
  A total of 14 unrelated Chinese HA subjects (FVIII activity <40%), 20 carrier subjects, three fetuses, and one PGD were included in this study. We first screened for the presence of FVIII intron 22 and intron 1 inversions. Second, the coding region of the FVIII gene was sequenced. For the novel mutations, FVIII mRNA expression was detected by real-time PCR and the protein structures were analyzed by bioinformatic tools.
  
  
  RESULTS
  Five novel mutations (c.1A>C, c.304_305insA, c.1594T>A, c.6045G>A, and c.2645_2646insG) were found. The real-time PCR showed that the expression of FVIII mRNAs was lower in HA patients than in normal subjects. Prenatal diagnosis and PGD were successfully performed: Two of three fetuses and four of eight blastomeres were confirmed to be normal.
  
  
  CONCLUSIONS
  In conclusion, genetic diagnosis of 14 unrelated HA subjects, 20 carrier subjects, three fetuses, and one PGD was successfully performed in our study.
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, GuangZhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital, Sun Yat-sen University, GuangZhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, GuangZhou, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Lin
authors.affiliation: The First Affiliated Hospital, Sun Yat-sen University, GuangZhou, China.
authors.forename: Y W
authors.initials: YW
authors.lastname: Xu
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, GuangZhou, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: He
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, GuangZhou, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, GuangZhou, China.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, GuangZhou, China.
authors.forename: W Y
authors.initials: WY
authors.lastname: Jiang
mesh_terms: D002681:China; D005169:Factor VIII / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D011296:Prenatal Diagnosis / Q000379:methods; D012333:RNA, Messenger / Q000097:blood
chemical_list: D012333:RNA, Messenger; D005169:Factor VIII
keywords: 
  FVIII
  ; Hemophilia A; gene diagnosis; novel mutation; preimplantation genetic diagnosis; prenatal diagnosis