MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION
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....
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doaj-751cac51bf564461bfb7e12aa0e4d6272020-11-25T00:10:52ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062018-09-01101e2018056e201805610.4084/mjhid.2018.0561782MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATIONMaimiza Zahari0Siti Aishah Sulaiman1Zulhabri Othman2Yasmin Ayob3Faraizah Abd Karim4Rahman Jamal5National Blood Centre, Jalan Tun Razak, Kuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Kuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Kuala Lumpur, MalaysiaNational Blood Centre, Jalan Tun Razak, Kuala Lumpur, MalaysiaNational Blood Centre, Jalan Tun Razak, Kuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Kuala Lumpur, MalaysiaBackground: 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.https://www.mjhid.org/index.php/mjhid/article/view/3479Factor VIIIFactor IXgenetic mutationHaemophilia AHaemophilia B |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maimiza Zahari Siti Aishah Sulaiman Zulhabri Othman Yasmin Ayob Faraizah Abd Karim Rahman Jamal |
spellingShingle |
Maimiza Zahari Siti Aishah Sulaiman Zulhabri Othman Yasmin Ayob Faraizah Abd Karim Rahman Jamal MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION Mediterranean Journal of Hematology and Infectious Diseases Factor VIII Factor IX genetic mutation Haemophilia A Haemophilia B |
author_facet |
Maimiza Zahari Siti Aishah Sulaiman Zulhabri Othman Yasmin Ayob Faraizah Abd Karim Rahman Jamal |
author_sort |
Maimiza Zahari |
title |
MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION |
title_short |
MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION |
title_full |
MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION |
title_fullStr |
MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION |
title_full_unstemmed |
MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION |
title_sort |
mutational profiles of f8 and f9 in a cohort of haemophilia a and haemophilia b patients in the multi-ethnic malaysian population |
publisher |
PAGEPress Publications |
series |
Mediterranean Journal of Hematology and Infectious Diseases |
issn |
2035-3006 |
publishDate |
2018-09-01 |
description |
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. |
topic |
Factor VIII Factor IX genetic mutation Haemophilia A Haemophilia B |
url |
https://www.mjhid.org/index.php/mjhid/article/view/3479 |
work_keys_str_mv |
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