Factor X Deficiency: Clinical Manifestation of 102 Subjects with Mutations in Factor 10 Gene

Abstract number: P1447

Herrmann¹ FH, Auerswald² G, Ruiz-Saez³ A, Navarette⁴ M, Pollmann⁵ H, Lopaciuk⁶ S, Batorova⁷ A, Wulff¹ K

¹¹University Greifswald, Institute of Human Genetics, Greifswald, Germany ¹¹University Greifswald, Institute of Human Genetics, Greifswald, Germany ²²Prof. Hess Children Hospital, Bremen, Germany ³³Centro Nacional de Hemofila, Banco municipal de Angre, Caracas, Venezuela ⁴⁴Children Hospital of CCSS, San Jose, Costa Rica ⁵⁵Institute of Thrombophilia and Hämostaseology, Münster, Germany ⁶⁶Institute of Hematology and Blood Transfusion, Warzaw, Germany ⁷⁷National Hemophilia Centre, Bratislava, Slovakia

Inherited Factor X deficiency (FXD) is a very rare (1 : 1 000 000) recessive bleeding disorder. The clinical phenotype correlates poorly with laboratory phenotype. For understanding the clinical manifestation in association with the causative genotype a detailed evaluation of the bleeding pattern in a high number of patients is needed. In an extensive international study the phenotype and the genotype of 102 subjects with mutations in F10 gene were analysed. The phenotype-genotype association was characterized. The pattern of symptoms of FXD is compared with 97 Factor VII deficient subjects. The bleeding symptoms were evaluated in detail. The molecular basis of the inherited FXD was analysed by sequencing of F10gene (coding regions, exon/intron boundaries, 5'flanking region). 28 homozygous, 7 compound heterozygous and 67 heterozygous FXD subjects are characterized, which are caused by 29 different mutations, 16 of which are novel. The pattern of spontaneous bleeding symptoms comprises easy bruising (55%), hematomas (43%), epistaxis (36%), hemarthrosis (33%), intracranial hemorrhage (ICH) (21%) and gastrointestinal hemorrhage (12%). Nine of 67 (13%) heterozygous subjects were symptomatic. For genotype-phenotype correlation 28 homozygous patients for 14 different mutations (6 of them novel mutations) were evaluated. ICH seems to be associated with Gly380Arg, and with the novel mutations IVS7-1G > A and Tyr163delAT. Extensive studies of FX- or FVII-deficient patients from various countries show that severe symptoms like ICH and hemarthrosis are significantly more frequent in FX than in FVII patients. The analysis of mutations provides the basis for genetic counselling.