A genetic analysis of 23 Chinese patients with hemophilia B.
Hemophilia B (HB) is an X-linked recessive bleeding disorder caused by mutations in the coagulation factor IX (FIX) gene. Genotyping patients with HB is essential for genetic counseling and provides useful information for patient management. In this study, the F9 gene from 23 patients with HB was analyzed by direct sequencing. Nineteen point mutations were identified, including a novel missense variant (c.520G > C, p.Val174Leu) in a patient with severe HB and a previously unreported homozygous missense mutation (c.571C > T, p.Arg191Cys) in a female patient with mild HB. Two large F9 gene deletions with defined breakpoints (g.10413_11363del, g.12163_23369del) were identified in two patients with severe HB using a primer walking strategy followed by sequencing. The flanking regions of the two breakpoints revealed recombination-associated elements (repetitive elements, non-B conformation forming motifs) with a 5-bp microhomology in the breakpoint junction of g.12163_23369del. These findings imply that non-homologous end joining and microhomology-mediated break-induced replication are the putative mechanisms for the deletions of the F9 gene. Because the g.12163_23369del deletion caused exons to be absent without a frameshift mutation occurring, a smaller FIX protein was observed in western blot analyses.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.|Collaborative Innovation Center of Hematology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Qing-Yun
QY
Wang
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.|Collaborative Innovation Center of Hematology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Bei
B
Hu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Hui
H
Liu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.|Collaborative Innovation Center of Hematology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Liang
L
Tang
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.|Collaborative Innovation Center of Hematology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Wei
W
Zeng
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Ying-Ying
YY
Wu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.|Collaborative Innovation Center of Hematology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Zhi-Peng
ZP
Cheng
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.|Collaborative Innovation Center of Hematology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yu
Y
Hu
D000328:Adult; D002675:Child, Preschool; D002681:China; D005164:Factor IX / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D017354:Point Mutation; D017384:Sequence Deletion / Q000235:genetics
D005164:Factor IX