Genetic analysis of haemophilia A in Taiwan

Y. C. Chen, S. H. Hu, S. N. Cheng, T. Y. Chao

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Haemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene. Identification of these mutations is becoming increasingly important in a variety of clinical settings. The purpose of this report is to describe our experience of FVIII gene mutation analysis in the largest cohort of patients in Taiwan including the discovery of 21 novel mutations. We tested 115 HA patients from 91 unrelated families, including 79 severe, 15 moderate and 21 mild types starting with an assay for the intron 22 inversion by long range-PCR followed if necessary by additional genetic studies. Intron 22 inversion accounted for 27.8% of the total and 36.7% of severe HA patients respectively while intron 1 inversion comprised 7.6% of severe patients. These were clearly different from the known data in caucasian populations. Of 75 patients without intron 22 or 1 inversion, 70 from 62 unrelated families revealed 56 different mutations by denaturing high-performance liquid chromatography (DHPLC), of which 21 were novel. Also, the only female patient with severe HA was found to have heterozygous non-sense mutation (c.6683G>A) of exon 24. Seven patients, including five without amplified PCR product and two without encoded DNA defect turned out to have exon(s) deletion or insertion by reverse transcript PCR (RT-PCR). In our study, the combination of various molecular techniques including LR-PCR, multiplex PCR, DHPLC and RT-PCR analysis enabled definitive detection of the causative FVIII gene defects in 112 of 113 (99%) HA patients.

Original languageEnglish
Pages (from-to)538-544
Number of pages7
JournalHaemophilia
Volume16
Issue number3
DOIs
Publication statusPublished - May 2010

Fingerprint

Hemophilia A
Taiwan
Introns
Mutation
Factor VIII
Polymerase Chain Reaction
Exons
High Pressure Liquid Chromatography
Genes
Multiplex Polymerase Chain Reaction
Hemorrhage
DNA
Population

Keywords

  • DHPLC
  • Factor VIII gene
  • Haemophilia A
  • Intron 1 inversion
  • Intron 22 inversion
  • Reverse transcript PCR

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Genetic analysis of haemophilia A in Taiwan. / Chen, Y. C.; Hu, S. H.; Cheng, S. N.; Chao, T. Y.

In: Haemophilia, Vol. 16, No. 3, 05.2010, p. 538-544.

Research output: Contribution to journalArticle

Chen, Y. C. ; Hu, S. H. ; Cheng, S. N. ; Chao, T. Y. / Genetic analysis of haemophilia A in Taiwan. In: Haemophilia. 2010 ; Vol. 16, No. 3. pp. 538-544.
@article{88820116fe8e494888e3d7a20b74c58c,
title = "Genetic analysis of haemophilia A in Taiwan",
abstract = "Haemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene. Identification of these mutations is becoming increasingly important in a variety of clinical settings. The purpose of this report is to describe our experience of FVIII gene mutation analysis in the largest cohort of patients in Taiwan including the discovery of 21 novel mutations. We tested 115 HA patients from 91 unrelated families, including 79 severe, 15 moderate and 21 mild types starting with an assay for the intron 22 inversion by long range-PCR followed if necessary by additional genetic studies. Intron 22 inversion accounted for 27.8{\%} of the total and 36.7{\%} of severe HA patients respectively while intron 1 inversion comprised 7.6{\%} of severe patients. These were clearly different from the known data in caucasian populations. Of 75 patients without intron 22 or 1 inversion, 70 from 62 unrelated families revealed 56 different mutations by denaturing high-performance liquid chromatography (DHPLC), of which 21 were novel. Also, the only female patient with severe HA was found to have heterozygous non-sense mutation (c.6683G>A) of exon 24. Seven patients, including five without amplified PCR product and two without encoded DNA defect turned out to have exon(s) deletion or insertion by reverse transcript PCR (RT-PCR). In our study, the combination of various molecular techniques including LR-PCR, multiplex PCR, DHPLC and RT-PCR analysis enabled definitive detection of the causative FVIII gene defects in 112 of 113 (99{\%}) HA patients.",
keywords = "DHPLC, Factor VIII gene, Haemophilia A, Intron 1 inversion, Intron 22 inversion, Reverse transcript PCR",
author = "Chen, {Y. C.} and Hu, {S. H.} and Cheng, {S. N.} and Chao, {T. Y.}",
year = "2010",
month = "5",
doi = "10.1111/j.1365-2516.2009.02180.x",
language = "English",
volume = "16",
pages = "538--544",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Genetic analysis of haemophilia A in Taiwan

AU - Chen, Y. C.

AU - Hu, S. H.

AU - Cheng, S. N.

AU - Chao, T. Y.

PY - 2010/5

Y1 - 2010/5

N2 - Haemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene. Identification of these mutations is becoming increasingly important in a variety of clinical settings. The purpose of this report is to describe our experience of FVIII gene mutation analysis in the largest cohort of patients in Taiwan including the discovery of 21 novel mutations. We tested 115 HA patients from 91 unrelated families, including 79 severe, 15 moderate and 21 mild types starting with an assay for the intron 22 inversion by long range-PCR followed if necessary by additional genetic studies. Intron 22 inversion accounted for 27.8% of the total and 36.7% of severe HA patients respectively while intron 1 inversion comprised 7.6% of severe patients. These were clearly different from the known data in caucasian populations. Of 75 patients without intron 22 or 1 inversion, 70 from 62 unrelated families revealed 56 different mutations by denaturing high-performance liquid chromatography (DHPLC), of which 21 were novel. Also, the only female patient with severe HA was found to have heterozygous non-sense mutation (c.6683G>A) of exon 24. Seven patients, including five without amplified PCR product and two without encoded DNA defect turned out to have exon(s) deletion or insertion by reverse transcript PCR (RT-PCR). In our study, the combination of various molecular techniques including LR-PCR, multiplex PCR, DHPLC and RT-PCR analysis enabled definitive detection of the causative FVIII gene defects in 112 of 113 (99%) HA patients.

AB - Haemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene. Identification of these mutations is becoming increasingly important in a variety of clinical settings. The purpose of this report is to describe our experience of FVIII gene mutation analysis in the largest cohort of patients in Taiwan including the discovery of 21 novel mutations. We tested 115 HA patients from 91 unrelated families, including 79 severe, 15 moderate and 21 mild types starting with an assay for the intron 22 inversion by long range-PCR followed if necessary by additional genetic studies. Intron 22 inversion accounted for 27.8% of the total and 36.7% of severe HA patients respectively while intron 1 inversion comprised 7.6% of severe patients. These were clearly different from the known data in caucasian populations. Of 75 patients without intron 22 or 1 inversion, 70 from 62 unrelated families revealed 56 different mutations by denaturing high-performance liquid chromatography (DHPLC), of which 21 were novel. Also, the only female patient with severe HA was found to have heterozygous non-sense mutation (c.6683G>A) of exon 24. Seven patients, including five without amplified PCR product and two without encoded DNA defect turned out to have exon(s) deletion or insertion by reverse transcript PCR (RT-PCR). In our study, the combination of various molecular techniques including LR-PCR, multiplex PCR, DHPLC and RT-PCR analysis enabled definitive detection of the causative FVIII gene defects in 112 of 113 (99%) HA patients.

KW - DHPLC

KW - Factor VIII gene

KW - Haemophilia A

KW - Intron 1 inversion

KW - Intron 22 inversion

KW - Reverse transcript PCR

UR - http://www.scopus.com/inward/record.url?scp=77953603802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953603802&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2516.2009.02180.x

DO - 10.1111/j.1365-2516.2009.02180.x

M3 - Article

C2 - 20236351

AN - SCOPUS:77953603802

VL - 16

SP - 538

EP - 544

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - 3

ER -