Mutational Profiles of F8 and F9 in a Cohort of Haemophilia A and Haemophilia B Patients in the Multi-ethnic Malaysian Population.

Autor:	Zahari M; National Blood Centre, Jalan Tun Razak, Kuala Lumpur, Malaysia., Sulaiman SA; UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Kuala Lumpur, Malaysia., Othman Z; UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Kuala Lumpur, Malaysia., Ayob Y; National Blood Centre, Jalan Tun Razak, Kuala Lumpur, Malaysia., Karim FA; National Blood Centre, Jalan Tun Razak, Kuala Lumpur, Malaysia., Jamal R; UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Kuala Lumpur, Malaysia.
Jazyk:	angličtina
Zdroj:	Mediterranean journal of hematology and infectious diseases [Mediterr J Hematol Infect Dis] 2018 Sep 01; Vol. 10 (1), pp. e2018056. Date of Electronic Publication: 2018 Sep 01 (Print Publication: 2018).
DOI:	10.4084/MJHID.2018.056
Abstrakt:	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 one 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. Competing Interests: Competing interests: The authors have declared that no competing interests exist.
Databáze:	MEDLINE
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