Abstract Number: PB1205
Meeting: ISTH 2020 Congress
Background: Rare bleeding disorders (RBD) are an inherited heterogeneous group of lower prevalence diseases, classified as fibrinogen disorders and several factor deficiencies (FD): FIID, FVD, FVIID, combined FV/FVIIID, FXD, FXID and FXIIID, which cause bleeding diathesis. The molecular characterization is only partial and genotype-phenotype correlation is not well known, mainly in FVIID.
Aims: To identify the pathogenic variants of RBD and the genotype-phenotype relationship in FVIID.
Methods: We have designed a prospective multicentre pilot Spanish study including 126 patients. Molecular characterization was performed in 82 patients by 23-gene panel using High-throughput sequencing (HTS), previously published. Bleeding score (BS) was evaluated by ISTH-BAT. Genotype-phenotype correlation was evaluated using the software package SPSS (v.25).
|Age (years)||30 (4-85)|
|Sex||Female: 53%, Male:45%|
|Severity||Mild: 67%, Moderate:6%, Severe: 11%, No data: 16%|
|RBD||FII: 1%(1), FV: 6%(8), FVII: 58%(73), FX: 5%(6), FXI: 11%(14), FXII: 2%(3), FXIII: 1%(1), FV+FVII: 1%(1), FV+FVIII: 1%(1), FV+FXI: 2%(2), Prekallikrein: 2%(2), Fibrinogen: 9%(11)|
|Pathogenic variants||Missense: 77%(63/82), Deletion: 10%(8/82), Nonsense: 7%(6/82), others: 6%(5/82)|
[Table 1. Baseline characteristics ]
Median age was 30 (range, 4-85); 53% was female; The most frequent RBD was FVIID (58%) and FXID 11%. Deficiencies were classified in mild (67%), moderate (6%), severe (11%). The median BS was 1 (0-22); the most frequent bleeding symptoms were mucocutaneous bleeding and epistaxis. 82 pathogenic variants were identified: 77% missense, 10% deletion, 7% nonsense, 6% others. Twenty-seven variants were novel. Forty-four patients are being sequenced to update the data for the congress. In the cohort of FVIID (n=73), most of them was classified in mild (73%), moderate (8%), severe (11%). Most of genetic variants affected to catalytic FVII domain (83%). Until, all FVII patients included, were sequenced, in the uni and multivariate analysis we found any correlation between genotype, BS and FVII levels (p>0.05).
Conclusions: We performed a pilot study to characterize the molecular-clinical-laboratory phenotype for RBDs in Spain. Molecular test was 100% successful and 27 novel variants were found. To date, we don´t find relationship phenotype and genotype in FVIID.
Funding: GRS 1650/A/17
To cite this abstract in AMA style:Rey Búa B, Bermejo N, Calvo JM, Martín-Salces M, Rodríguez Alen A, Dávila J, Pérez Sánchez M, Martín Antoran JM, García Díaz C, Benito R, Del Rey M, Hernández-Rivas JM, González-Porras JR, Bastida JM. Genotype and Phenotype Characterization in RBDs: A Spanish Pilot Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/genotype-and-phenotype-characterization-in-rbds-a-spanish-pilot-study/. Accessed December 3, 2021.
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