F8 inversions of introns 22 and 1 confer a moderate risk of inhibitors in Mexican patients with severe hemophilia A. Concordance analysis and literature review
Copyright © 2018 Elsevier Inc. All rights reserved..
Intron-22 (Inv22) and intron-1 (Inv1) inversions account for approximately one half of all severe cases of hemophilia A (SHA) worldwide. Inhibitor development against exogenous factor VIII (FVIII) represents a major complication in HA. The causative F8 mutation is considered the most decisive factor conditioning inhibitor development. We aimed to investigate prevalence of Inv22 and Inv1 mutations, and its association as risk factors for developing inhibitors to FVIII. We investigated Inv22 and Inv1 in 255 SHA Mexican patients from 193 unrelated families using the inverse shifting-polymerase chain reaction (IS-PCR). We analyzed the association between inversions and inhibitor development via logistic regression introducing as covariates the populations, the inversions, F8-haplotypes and the age of patients at enrollment. Inv22 was found in 91/193 (47.2%: 38.9% exhibited Inv22-1 and 8.3% Inv22-2), and Inv1 in 2/193 (1.0%) independent families. Absolute inhibitor prevalence (IP) for Inv22 in unrelated patients was 15% (10-19). The cohorts and age of patients were independent predictors of inhibitor risk, but not inversions or haplotypes. Inversions presence in our population was associated to a moderate risk of developing inhibitors. Inv1 was found for the first time in two Mexican families. A relevant genetic component was observed by the strong concordance among brother-pairs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Blood cells, molecules & diseases - 71(2018) vom: 12. Juli, Seite 45-52 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Luna-Záizar, Hilda [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.03.2019 Date Revised 21.03.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bcmd.2018.02.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM282007091 |
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| 245 | 1 | 0 | |a F8 inversions of introns 22 and 1 confer a moderate risk of inhibitors in Mexican patients with severe hemophilia A. Concordance analysis and literature review |
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| 520 | |a Copyright © 2018 Elsevier Inc. All rights reserved. | ||
| 520 | |a Intron-22 (Inv22) and intron-1 (Inv1) inversions account for approximately one half of all severe cases of hemophilia A (SHA) worldwide. Inhibitor development against exogenous factor VIII (FVIII) represents a major complication in HA. The causative F8 mutation is considered the most decisive factor conditioning inhibitor development. We aimed to investigate prevalence of Inv22 and Inv1 mutations, and its association as risk factors for developing inhibitors to FVIII. We investigated Inv22 and Inv1 in 255 SHA Mexican patients from 193 unrelated families using the inverse shifting-polymerase chain reaction (IS-PCR). We analyzed the association between inversions and inhibitor development via logistic regression introducing as covariates the populations, the inversions, F8-haplotypes and the age of patients at enrollment. Inv22 was found in 91/193 (47.2%: 38.9% exhibited Inv22-1 and 8.3% Inv22-2), and Inv1 in 2/193 (1.0%) independent families. Absolute inhibitor prevalence (IP) for Inv22 in unrelated patients was 15% (10-19). The cohorts and age of patients were independent predictors of inhibitor risk, but not inversions or haplotypes. Inversions presence in our population was associated to a moderate risk of developing inhibitors. Inv1 was found for the first time in two Mexican families. A relevant genetic component was observed by the strong concordance among brother-pairs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a F8 gene inversions | |
| 650 | 4 | |a FVIII inhibitors | |
| 650 | 4 | |a Familial concordance | |
| 650 | 4 | |a Inhibitor risk factors | |
| 650 | 4 | |a Severe Hemophilia A | |
| 650 | 7 | |a Blood Coagulation Factor Inhibitors |2 NLM | |
| 650 | 7 | |a Isoantibodies |2 NLM | |
| 650 | 7 | |a Factor VIII |2 NLM | |
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| 700 | 1 | |a González-Alcázar, José Ángel |e verfasserin |4 aut | |
| 700 | 1 | |a Evangelista-Castro, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Aguilar-López, Lilia Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Ruiz-Quezada, Sandra Luz |e verfasserin |4 aut | |
| 700 | 1 | |a Beltrán-Miranda, Claudia Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Jaloma-Cruz, Ana Rebeca |e verfasserin |4 aut | |
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