Original Articles
Vol. 10 (2018): Review Articles, Original Articles, Scientific Letters, Case Reports
MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: May 17, 2018
Accepted: August 10, 2018
Accepted: August 10, 2018
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Hematology
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Background: Haemophilia A (HA) and Haemophilia B (HB) are X-linked blood disorders that are caused by various mutations in the factor VIII (F8) and factor IX (F9) genes respectively. Identification of mutations is essential as some of the mutations are associated with the development of inhibitors. This study is the first comprehensive study of the F8 mutational profile in Malaysia.
Materials and methods: We analysed 100 unrelated HA and 15 unrelated HB patients for genetic alterations in the F8 and F9 genes by using the long-range PCR, DNA sequencing, and the multiplex-ligation-dependent probe amplification assays. The prediction software was used to confirm the effects of these mutations on factor VIII and IX proteins.
Results: 44 (53%) of the severe HA patients were positive for F8 intron 22 inversion, and three (3.6%) were positive for intron 1 inversion. There were 22 novel mutations in F8, including missense (8), frameshift (9), splice site (3), large deletion (1) and nonsense (1) mutations. In HB patients, four novel mutations were identified including the splice site (1), small deletion (1), large deletion (1) and missense (1) mutation.
Discussion: The mutational spectrum of F8 in Malaysian patients is heterogeneous, with a slightly higher frequency of intron 22 inversion in these severe HA patients when compared to other Asian populations. Identification of these mutational profiles in F8 and F9 genes among Malaysian patients will provide a useful reference for the early detection and diagnosis of HA and HB in the Malaysian population.
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Original ArticlesHow to Cite
“MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION” (2018) Mediterranean Journal of Hematology and Infectious Diseases, 10(1), p. e2018056. doi:10.4084/mjhid.2018.056.
