Exploration of the genetic basis of coagulation factor VII deficiency in a Maltese family

Abstract

Congenital coagulation Factor VII deficiency is a rare coagulation disorder charterised by haemorrhages occurring spontaneously in the severely deficient patient or after surgical challenge in those who are mildly affected (Mariani et aI., 1978). Factor VII deficiency is characteristically inherited in an autosomal recessive manner. The frequency of this disorder has been estimated to be one per 500,000 persons worldwide. Definitive diagnosis of Factor VII deficiency rests on a specific assay for Factor VII coagulant activity (functional analysis), or for Factor VII antigen level (immunochemical analysis), or both. Functional variants of Factor VII have been described based on different reactivity with tissue thromboplastins from several species (Roberts and Foster, 1987). Factor VII deficiency in Malta was first identified in a single family in July 1991. The proband was a girl born in 1987. She had no history of bleeding tendency and Factor VII deficiency was diagnosed during preoperative coagulation studies prior to tonsillectomy. Studies were performed in order to explore the genetic basis of coagulation Factor VII deficiency in this Maltese kindred. Factor VII coagulant assays were performed on 11 members of the kindred. These assays were performed four times on plasma samples from the proband, siblings and parents, employing a tissue thromboplastin from a different species each time. The thromboplastins were ox, porcine, human and rabbit, brain tissue thromboplastin. Factor VII coagulant assays were performed once on plasma samples from other members of the kindred, employing rabbit brain tissue thromboplastin. A molecular probe capable of hybridising with the Factor VII gene and suitable for mapping DNA abnormalities of the same gene was synthesised. Genomic DNA was isolated from the leukocytes of a peripheral blood sample from 16 members of the affected kindred. These genomic DNA samples were stored for future analysis utilising the synthesised probe.