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

Publication date: Available online 23 February 2018 Source:Blood Cells, Molecules, and Diseases Author(s): Hilda Luna-Záizar, José Ángel González-Alcázar, Natalia Evangelista-Castro, Lilia Beatriz Aguilar-López, Sandra Luz Ruiz-Quezada, Claudia Patricia Beltrán-Miranda, Ana Rebeca Jaloma-Cruz 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 popu...
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research