info:eu-repo/semantics/article
Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
Fecha
2018-03Registro en:
Abelleyro, Miguel Martin; Marchione, Vanina Daniela; Elhelou, L.; Radic, Claudia Pamela; Rossetti, Liliana Carmen; et al.; Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation; Thieme Medical Publ Inc; Thrombosis and Haemostasis; 118; 3; 3-2018; 617-620
0340-6245
CONICET Digital
CONICET
Autor
Abelleyro, Miguel Martin
Marchione, Vanina Daniela
Elhelou, L.
Radic, Claudia Pamela
Rossetti, Liliana Carmen
Nemec, Diego Martín
de Brasi, Carlos Daniel
Resumen
Large F8 deletions cause 10-15% of severe-Haemophilia A (HA) cases and associate with the highest clinical/biochemical severity and with significantly augmented risks for developing inhibitors against therapeutic FVIII. Only 45-50% of severe-HA cases present family history of the disease. In the remnant cases (sporadic-HA), the mutation origin defines different clinical scenarios in which the risk of recurrence and thus genetic counselling significantly vary. The origin of the causative mutation may be either pre-zygotic or post-zygotic generating a genetic mosaicism affecting, partially or totally, one or more tissue/organs including the gonads. Furthermore, the technical features of the genotyping approach for detecting and measuring an eventual genetic mosaicism critically affect its diagnosis. The quali-quantitative extent of somatic and germinal mosaicisms is passively assumed to be associated with the phenotypic expression of haemophilia severity and inheritance pattern, respectively. We present a case of a family affected with HA in which the clinical/biochemical severity and inheritance patterns associate with the observed fraction of mosaic cells bearing a F8-promoter deletion.