PB0217 - Genotypic distribution in congenital rare bleeding disorders patients of Asian Indian origin: Results of a collaborative ISTH-RTC study

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

Amit Sharma, PhD

Post Doctoral Researcher
All India Institute of Medical Sciences
New Delhi, Delhi, India
SS

Sneha Singh, PhD (she/her/hers)

Postdoctoral researcher
Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn
Bonn, Nordrhein-Westfalen, Germany

Co-Author(s)

Behnaz Pezeshkpoor, PhD (she/her/hers)

Group Leader
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
AP

Anna Pavlova

Senior Physician
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
Samhitha Urs Ramaraje Urs, MSc

PhD Student
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn
Bonn, Nordrhein-Westfalen, Germany

Presenting Author(s)

Haroon Javed, MSc

PhD student
Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn
Bonn, Nordrhein-Westfalen, Germany

Co-Author(s)

Kamal Kishor, PhD

Post Doctorate fellow
All India Institute of Medical Sciences
New Delhi, Delhi, India
Ravi Ranjan, PhD

Scientist
ALL INDIA INSTITUT OF MEDICAL SCIENCES, NEW DELHI
New Delhi, Delhi, India
MM

Manoranjan Mahapatra

Professor Of Hematology
AIIMS NEW DELHI
DELHI, Delhi, India
Johannes Oldenburg, MD (he/him/his)

Professor, Chairman and Director
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
Arijit Biswas, PD Dr (Biol)

Scientist
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn
Bonn, Nordrhein-Westfalen, Germany

Background: Rare bleeding disorders (RBDs) are autosomal recessive, hemorrhagic disorders with an estimated frequency from 1:500000 to 1:2 million. Molecular defects in their corresponding genes are the main cause and identifying/characterizing these defects aids in the diagnosis, treatment, and management of RBDs

Aims: To identify the underlying genetic defects in a cohort of RBDs patients by next-generation sequencing

Methods: A total of 48 patients with congenital deficiencies of FVII (n=20), FXIII (n=13), FV (n=5), FX (n=5), fibrinogen (n=3), and one each of FII, FV&FX combined deficiency were recruited. Coagulation profiling was done for all the patients. Deficiency of FII, FV, FVII, and FX was confirmed by the one-stage clotting method. Fibrinogen activity was assessed by Clauss clotting method. A clot solubility assay was performed for FXIII deficiency. Targeted next-generation sequencing was done on a MiSeq platform

Results: The median age of patients was 18 (range 2-72 years) with an almost proportionate distribution between the sexes (M:22 & F:24). The FVII deficient patients showed activity levels between < 1% to 45%. All patients with FXIII deficiency were clot solubility assay positive. Patients with other deficiencies showed activity levels between < 1-3% for FV and < 1-1.5% for FX. One FII patient showed activity levels of 1.2% while a patient with combined FV&FX deficiency had FV levels < 1% and FX levels of 1.6%. A total of 28 pathogenic variants were identified; of them, 11 were novel (F13A1:5, F7:2, FGA:2, F10:1 & F5:1) and their distributions shown in Table 1

Conclusion(s): In our RBDs cohort, the highest number of novel genetic defects (n=5) were detected in FXIII deficient patients even though the maximum number of patients were of FVII deficiency. All novel mutations in FXIII deficient patients were detected in the F13A1 gene. Missense mutations dominated the genotypic distribution (>60% of all detected mutations) among RBDs cohort