title: [Gene analysis and pathogenesis in 40 patients with hemophilia B].
abstract: Hemophilia B (HB) is a recessive X-linked inherited disorder, the pathogenesis of HB is deficiency or functional abnormalities of coagulation factor IX, which is caused by F9 gene mutations. To explore the mechanism of its molecular pathology, 40 patients with HB were studied with polymerase chain reaction (PCR) and direct sequencing. The diagnosis of HB patients were based on clinical manifestation and deficient factor IX activity in plasma. DNA was routinely extracted from peripheral blood cells of the patients and their relatives, all the 8 exons and their flanking boundaries were amplified by PCR, and the PCR products were screened by direct sequencing. Mutations which were found in study need to exclude polymorphism. The results showed that 34 mutations were confirmed in 40 HB patients, including 6 nonsense mutations, 24 missense mutations, 2 splice site mutations and 2 frame mutations for 1 or 2 nucleotide insertion. After retrieved, 4 missense mutations and 1 frameshift mutation were found for the first time. Among the 34 mutations, 2 mutations in signal peptide, 7 mutations in propeptide and gla domain, 7 mutations in epidermal growth factor-like domain, 3 mutations in activation domain, 15 mutations in serine protease or catalytic domain. It is concluded that gene analysis can directly explain molecular mechanism of hemophilia B and also provides the foundation for further studies to the function of coagulation factor IX. There is obvious heterogeneity in F9 gene mutation and missense mutation is still the main way of mutation, which are closely related to clinical features. DNA sequencing and linkage analysis are efficient methods for HB carriers and prenatal gene diagnosis.
authors.affiliation: Jiangsu Institute of Hemtology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province,China.
authors.forename: Chao-Rong
authors.initials: CR
authors.lastname: Wang
authors.forename: Zi-Qiang
authors.initials: ZQ
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Xia
authors.initials: X
authors.lastname: Bai
authors.forename: Chang-Geng
authors.initials: CG
authors.lastname: Ruan
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005164:Factor IX / Q000235:genetics; D002836:Hemophilia B / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male
chemical_list: D005164:Factor IX