PB1285 - A novel mutation of haemophilia C in a kindred: a F11 splice site variant

Background: A patient having factor XI deficiency - also known as haemophilia C or Rosenthal syndrome - an inherited coagulation disorder leading to bleeding tendency, was identified in the haematology clinic and recruited for a family study. It has been well reported that the spectrum of gene variants in factor XI deficiency is highly heterogeneous and varies amongst different ethnicities. It is suspected that this kindred harbour a novel variant of the F11 gene.

Aims: This study aims to identify and characterise the F11 variant that results in factor XI deficiency with the clinical and laboratory features in this kindred.

Methods: The participants completed the ISTH-BAT structured questionnaires to evaluate and document their historical bleeding risks and symptoms and underwent blood tests (including clotting screen, specific factor assay, mixing study) in a hospital haematology laboratory. Genetic study was performed for sequencing their genomic and complementary DNA in order to identify the gene variant and the consequent transcript alteration.

Results: The affected participants returned increased scores on ISTH-BAT questionnaires and showed abnormal clotting screens with isolated prolonged APTT and borderline reduced factor XI activity (~40%). The proband was found to be heterozygous for a donor splice site mutation c.865+2 T>C.

Conclusion(s): Genetic sequencing of the DNA sample revealed a novel splice site variant (F11 c.865+2 T>C) which was regarded to be likely pathogenic. It reiterates the genetic heterogeneity of factor XI deficiency and heralds the application of genetic techniques for personalised diagnostics in the context of rare bleeding disorders.