Somatic/germinal mosaicism of a F8 promoter deletion confounds clinical predictions in a family with haemophilia A: key role of genotype quantitation

MIGUEL M. ABELLEYRO; VANINA D. MARCHIONE; LUDMILA ELHELOU; CLAUDIA P. RADIC; LILIANA C. ROSSETTI; DANIELA NEME; CARLOS D. DE BRASI

THROMBOSIS AND HAEMOSTASIS

SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN

Lugar: Stuttgart ; Año: 2018 vol. 118 p. 617 - 620

0340-6245

Large F8 deletions caused 10-15% of severe-Hemophilia A (HA) cases and were associated with the highest severity and significantly augmented risks for developing inhibitors against therapeutic FVIII [1]. Only 45-50% of severe-HA cases present family history of the disease [2]. In the remnant cases (sporadic-HA), the origin of the hemophilia-causative mutation defines different clinical scenarios in which the risk of recurrence, and thus the genetic counseling varies. 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 [3]. The quali-quantitative extent of the somatic and germinal mosaicisms are believe to be associated with the phenotypic expression of hemophilia severity and inheritance pattern, respectively. We present a case of a family affected with HA in which the clinical/biochemical severity and inheritance pattern seem to be associated with the observed fraction of mosaic cells bearing a F8-promoter deletion.