F8 GENOTYPE CHARACTERISATION OF THE FIRST ARGENTINE SERIES OF PATIENTS WITH MILD HAEMOPHILIA A: NOTABLE PREVALENCE OF RECURRENT MUTATIONS.

MARCHIONE, VANINA DANIELA; RADIC, CLAUDIA PAMELA; ABELLEYRO, MIGUEL MARTÍN; RODRIGUEZ R; SANCHEZ LUCERO, ANALIA; NEME, DANIELA; DE BRASI, CARLOS DANIEL; ROSSETTI, LILIANA CARMEN

Mar del Plata

Congreso; Reunión Conjunta LXIII Sociedad Argentina de Investigación Clínica (SAIC) - LXVI Sociedad Argentina de Inmunología (SAI) ? Sociedad Argentina de Fisiología (SAFIS); 2018

Abstract:Haemophilia A (HA) is the commonest X-linked coagulopathy caused by deleterious mutations in F8. Mild-HA associates with minor reduction in the clotting activity of factor VIII (FVIII:C) to 5-40 UI/dL. Perhaps due to their mild phenotype expression, mild-HA patients are rarely genotyped although they represent 35-40% of HA cases worldwide. The scarce published data indicate that mild-HA shows notable differences with severe-HA (FVIII:CA (n=3), the Dup13* (n=3) and a synonym change (n=2) (*reported with Italian origin). Non-recurrent mutations included 24 missense, an ins-del and two splicing defects. Our findings demonstrate that our practical approach is adequate to characterise the mild-HA-causative F8-genotype in patients and relatives, highlight the prevalence of missense defects in mild-HA (50/61, 82%) and indicate that the higher frequency assessed for recurrent mutations in mild-HA respect to severe-HA may reflect the higher mutational turnover of the severe-HA pool.