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

Overview

Journal Mediterr J Hematol Infect Dis

Specialty Infectious Diseases

Date 2018 Sep 14

PMID 30210749

Citations 4

Authors

Maimiza Zahari

Siti Aishah Sulaiman

Zulhabri Othman

Yasmin Ayob

Faraizah Abd Karim

Rahman Jamal

Affiliations

Soon will be listed here.

Abstract

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 mutational profile in Malaysia.

Materials And Methods: We analysed 100 unrelated HA and 15 unrelated HB patients for genetic alterations in the and 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 intron 22 inversion, and three (3.6%) were positive for intron one inversion. There were 22 novel mutations in , 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 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 and 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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