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coding region of the respective factor gene was performed and 12 (haemophilia A) and 5 (haemophilia B) previously unpublished disease-causing mutations were identified.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 language | English |
|---|---|
| Pages (from-to) | 161-166 |
| Number of pages | 6 |
| Journal | Blood Coagulation and Fibrinolysis |
| Volume | 26 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 6 2015 |
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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 journal › Article
}
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 -