Carrier and prenatal diagnostic strategy and newly identified mutations in Hungarian haemophilia A and B families

András Bors, H. Andrikovics, Zsuzsanna Illés, Rita Jáger, Mária Kardos, Anikó Marosi, L. Nemes, A. Tordai

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Deficiencies of blood coagulation factors VIII and IX (haemophilia A and haemophilia B) represent the most common inherited bleeding disorders with a wide range of causative mutations. Carrier and prenatal diagnostics are preferably performed by direct mutation detection; however, in certain situations, indirect family studies may also be useful. We aimed to utilize a combination of direct and indirect techniques for carrier and prenatal diagnostics in both haemophilias in a single national centre. Two hundred and eleven haemophilia A families were investigated by screening for inversions of introns 1 and 22, and by family studies using polymorphic markers. Twenty-eight haemophilia A and 39 haemophilia B families were investigated by Sanger-sequencing of the coding regions. Among severe haemophilia A families, frequencies of intron 22 and 1 inversions were 82 out of 145 (57%) and two out of 145 (1.4%). Sequencing of the entire coding region of the respective factor gene was performed and 12 (haemophilia A) and 5 (haemophilia B) previously unpublished disease-causing mutations were identified. For genetic markers used for haemophilia A indirect family testing, heterozygosity rates varied between 137 out of 327 [42% intragenic BclI restriction fragment length polymorphism (RFLP], 168 out of 254 (66% intragenic F8Civs13CA) and 202 out of 261 (77% extragenic DXS15CA) with a combined rate of 92% (intragenic markers) and 97% (all three markers). For male fetuses, prenatal diagnostics was provided to 43 haemophilia A families (n=22 with direct mutation detection and n=21 by indirect family testing) and to three haemophilia B families. The combination of direct and indirect molecular genetics approaches is a successful and cost-effective approach to provide carrier and prenatal diagnostics and risk assessment for inhibitor formation.

Original languageEnglish
Pages (from-to)161-166
Number of pages6
JournalBlood Coagulation and Fibrinolysis
Volume26
Issue number2
DOIs
Publication statusPublished - Mar 6 2015

Fingerprint

Hemophilia B
Hemophilia A
Mutation
Restriction Fragment Length Polymorphisms
Introns
Factor IX
Factor VIII
Genetic Markers
Molecular Biology
Fetus
Hemorrhage
Costs and Cost Analysis

Keywords

  • carrier
  • genetics
  • haemophilia A
  • haemophilia B
  • indirect marker
  • mutation
  • prenatal diagnostics

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

Carrier and prenatal diagnostic strategy and newly identified mutations in Hungarian haemophilia A and B families. / Bors, András; Andrikovics, H.; Illés, Zsuzsanna; Jáger, Rita; Kardos, Mária; Marosi, Anikó; Nemes, L.; Tordai, A.

In: Blood Coagulation and Fibrinolysis, Vol. 26, No. 2, 06.03.2015, p. 161-166.

Research output: Contribution to journalArticle

Bors, András ; Andrikovics, H. ; Illés, Zsuzsanna ; Jáger, Rita ; Kardos, Mária ; Marosi, Anikó ; Nemes, L. ; Tordai, A. / Carrier and prenatal diagnostic strategy and newly identified mutations in Hungarian haemophilia A and B families. In: Blood Coagulation and Fibrinolysis. 2015 ; Vol. 26, No. 2. pp. 161-166.
@article{67b0bc9f6762451bbebefe08aeea2543,
title = "Carrier and prenatal diagnostic strategy and newly identified mutations in Hungarian haemophilia A and B families",
abstract = "Deficiencies of blood coagulation factors VIII and IX (haemophilia A and haemophilia B) represent the most common inherited bleeding disorders with a wide range of causative mutations. Carrier and prenatal diagnostics are preferably performed by direct mutation detection; however, in certain situations, indirect family studies may also be useful. We aimed to utilize a combination of direct and indirect techniques for carrier and prenatal diagnostics in both haemophilias in a single national centre. Two hundred and eleven haemophilia A families were investigated by screening for inversions of introns 1 and 22, and by family studies using polymorphic markers. Twenty-eight haemophilia A and 39 haemophilia B families were investigated by Sanger-sequencing of the coding regions. Among severe haemophilia A families, frequencies of intron 22 and 1 inversions were 82 out of 145 (57{\%}) and two out of 145 (1.4{\%}). Sequencing of the entire coding region of the respective factor gene was performed and 12 (haemophilia A) and 5 (haemophilia B) previously unpublished disease-causing mutations were identified. For genetic markers used for haemophilia A indirect family testing, heterozygosity rates varied between 137 out of 327 [42{\%} intragenic BclI restriction fragment length polymorphism (RFLP], 168 out of 254 (66{\%} intragenic F8Civs13CA) and 202 out of 261 (77{\%} extragenic DXS15CA) with a combined rate of 92{\%} (intragenic markers) and 97{\%} (all three markers). For male fetuses, prenatal diagnostics was provided to 43 haemophilia A families (n=22 with direct mutation detection and n=21 by indirect family testing) and to three haemophilia B families. The combination of direct and indirect molecular genetics approaches is a successful and cost-effective approach to provide carrier and prenatal diagnostics and risk assessment for inhibitor formation.",
keywords = "carrier, genetics, haemophilia A, haemophilia B, indirect marker, mutation, prenatal diagnostics",
author = "Andr{\'a}s Bors and H. Andrikovics and Zsuzsanna Ill{\'e}s and Rita J{\'a}ger and M{\'a}ria Kardos and Anik{\'o} Marosi and L. Nemes and A. Tordai",
year = "2015",
month = "3",
day = "6",
doi = "10.1097/MBC.0000000000000212",
language = "English",
volume = "26",
pages = "161--166",
journal = "Blood Coagulation and Fibrinolysis",
issn = "0957-5235",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Carrier and prenatal diagnostic strategy and newly identified mutations in Hungarian haemophilia A and B families

AU - Bors, András

AU - Andrikovics, H.

AU - Illés, Zsuzsanna

AU - Jáger, Rita

AU - Kardos, Mária

AU - Marosi, Anikó

AU - Nemes, L.

AU - Tordai, A.

PY - 2015/3/6

Y1 - 2015/3/6

N2 - Deficiencies of blood coagulation factors VIII and IX (haemophilia A and haemophilia B) represent the most common inherited bleeding disorders with a wide range of causative mutations. Carrier and prenatal diagnostics are preferably performed by direct mutation detection; however, in certain situations, indirect family studies may also be useful. We aimed to utilize a combination of direct and indirect techniques for carrier and prenatal diagnostics in both haemophilias in a single national centre. Two hundred and eleven haemophilia A families were investigated by screening for inversions of introns 1 and 22, and by family studies using polymorphic markers. Twenty-eight haemophilia A and 39 haemophilia B families were investigated by Sanger-sequencing of the coding regions. Among severe haemophilia A families, frequencies of intron 22 and 1 inversions were 82 out of 145 (57%) and two out of 145 (1.4%). Sequencing of the entire coding region of the respective factor gene was performed and 12 (haemophilia A) and 5 (haemophilia B) previously unpublished disease-causing mutations were identified. For genetic markers used for haemophilia A indirect family testing, heterozygosity rates varied between 137 out of 327 [42% intragenic BclI restriction fragment length polymorphism (RFLP], 168 out of 254 (66% intragenic F8Civs13CA) and 202 out of 261 (77% extragenic DXS15CA) with a combined rate of 92% (intragenic markers) and 97% (all three markers). For male fetuses, prenatal diagnostics was provided to 43 haemophilia A families (n=22 with direct mutation detection and n=21 by indirect family testing) and to three haemophilia B families. The combination of direct and indirect molecular genetics approaches is a successful and cost-effective approach to provide carrier and prenatal diagnostics and risk assessment for inhibitor formation.

AB - Deficiencies of blood coagulation factors VIII and IX (haemophilia A and haemophilia B) represent the most common inherited bleeding disorders with a wide range of causative mutations. Carrier and prenatal diagnostics are preferably performed by direct mutation detection; however, in certain situations, indirect family studies may also be useful. We aimed to utilize a combination of direct and indirect techniques for carrier and prenatal diagnostics in both haemophilias in a single national centre. Two hundred and eleven haemophilia A families were investigated by screening for inversions of introns 1 and 22, and by family studies using polymorphic markers. Twenty-eight haemophilia A and 39 haemophilia B families were investigated by Sanger-sequencing of the coding regions. Among severe haemophilia A families, frequencies of intron 22 and 1 inversions were 82 out of 145 (57%) and two out of 145 (1.4%). Sequencing of the entire coding region of the respective factor gene was performed and 12 (haemophilia A) and 5 (haemophilia B) previously unpublished disease-causing mutations were identified. For genetic markers used for haemophilia A indirect family testing, heterozygosity rates varied between 137 out of 327 [42% intragenic BclI restriction fragment length polymorphism (RFLP], 168 out of 254 (66% intragenic F8Civs13CA) and 202 out of 261 (77% extragenic DXS15CA) with a combined rate of 92% (intragenic markers) and 97% (all three markers). For male fetuses, prenatal diagnostics was provided to 43 haemophilia A families (n=22 with direct mutation detection and n=21 by indirect family testing) and to three haemophilia B families. The combination of direct and indirect molecular genetics approaches is a successful and cost-effective approach to provide carrier and prenatal diagnostics and risk assessment for inhibitor formation.

KW - carrier

KW - genetics

KW - haemophilia A

KW - haemophilia B

KW - indirect marker

KW - mutation

KW - prenatal diagnostics

UR - http://www.scopus.com/inward/record.url?scp=84922398519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922398519&partnerID=8YFLogxK

U2 - 10.1097/MBC.0000000000000212

DO - 10.1097/MBC.0000000000000212

M3 - Article

C2 - 25255241

AN - SCOPUS:84922398519

VL - 26

SP - 161

EP - 166

JO - Blood Coagulation and Fibrinolysis

JF - Blood Coagulation and Fibrinolysis

SN - 0957-5235

IS - 2

ER -