Mutational profiles of F8 and F9 in a cohort of Haemophilia A and Haemophilia B patients in the multi-ethnic Malaysian population

Maimiza Zahari, Siti Aishah Sulaiman, Zulhabri Othman, Yasmin Ayob, Faraizah Abd Karim, A. Rahman A. Jamal

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Article numbere2018056
JournalMediterranean Journal of Hematology and Infectious Diseases
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Hemophilia B
Hemophilia A
Mutation
Introns
Population
Factor IX
Factor VIII
Genes
RNA Splice Sites
Nonsense Codon
Multiplex Polymerase Chain Reaction
Malaysia
Missense Mutation
DNA Sequence Analysis
Early Diagnosis
Software
Polymerase Chain Reaction
Proteins

Keywords

  • Factor IX
  • Factor VIII
  • Genetic mutation
  • Haemophilia A
  • Haemophilia B

ASJC Scopus subject areas

  • Hematology
  • Infectious Diseases

Cite this

Mutational profiles of F8 and F9 in a cohort of Haemophilia A and Haemophilia B patients in the multi-ethnic Malaysian population. / Zahari, Maimiza; Sulaiman, Siti Aishah; Othman, Zulhabri; Ayob, Yasmin; Karim, Faraizah Abd; A. Jamal, A. Rahman.

In: Mediterranean Journal of Hematology and Infectious Diseases, Vol. 10, No. 1, e2018056, 01.01.2018.

Research output: Contribution to journalArticle

@article{a650dbe13ede48a3906574b6f9db701e,
title = "Mutational profiles of F8 and F9 in a cohort of Haemophilia A and Haemophilia B patients in the multi-ethnic Malaysian population",
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 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.",
keywords = "Factor IX, Factor VIII, Genetic mutation, Haemophilia A, Haemophilia B",
author = "Maimiza Zahari and Sulaiman, {Siti Aishah} and Zulhabri Othman and Yasmin Ayob and Karim, {Faraizah Abd} and {A. Jamal}, {A. Rahman}",
year = "2018",
month = "1",
day = "1",
doi = "10.4084/MJHID.2018.056",
language = "English",
volume = "10",
journal = "Mediterranean Journal of Hematology and Infectious Diseases",
issn = "2035-3006",
publisher = "Universita Cattolica del Sacro Cuore",
number = "1",

}

TY - JOUR

T1 - Mutational profiles of F8 and F9 in a cohort of Haemophilia A and Haemophilia B patients in the multi-ethnic Malaysian population

AU - Zahari, Maimiza

AU - Sulaiman, Siti Aishah

AU - Othman, Zulhabri

AU - Ayob, Yasmin

AU - Karim, Faraizah Abd

AU - A. Jamal, A. Rahman

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Factor IX

KW - Factor VIII

KW - Genetic mutation

KW - Haemophilia A

KW - Haemophilia B

UR - http://www.scopus.com/inward/record.url?scp=85056577876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056577876&partnerID=8YFLogxK

U2 - 10.4084/MJHID.2018.056

DO - 10.4084/MJHID.2018.056

M3 - Article

VL - 10

JO - Mediterranean Journal of Hematology and Infectious Diseases

JF - Mediterranean Journal of Hematology and Infectious Diseases

SN - 2035-3006

IS - 1

M1 - e2018056

ER -