Prenatal Diagnosis in a Lebanese Family with Severe Factor VII Deficiency

Abstract number: P0751

Farah¹ RA, Zalloua² P, Chammas¹ M, Schved³ JF, Giansily-Blaizot³ M

¹¹Departments of Pediatrics and Obstetrics, Rizk Hospital, Beirut, Lebanon ¹¹Departments of Pediatrics and Obstetrics, Rizk Hospital, Beirut, Lebanon ²²Departments of Genetics, American University of Beirut, Beirut, Lebanon ³³CHU Saint Eloi, Montpellier, France

Factor VII (FVII) deficiency is a rare inherited bleeding disorder. Several causative mutations have been identified with a variety of clinical spectrums. We report a Lebanese family with first degree consanguinity that had a first child with oral mucosal bleeding and rectorrhagia since the age of 1 month. Laboratory work-up showed markedly prolonged PT (54 sec) with an INR of 5.5. aPTT, Fibrinogen, renal and liver function studies were normal. Factor VII level was 10%. At the age of 4 months, she presented with sudden onset of projectile vomiting, bulging fontanels, lethargy and decreased alertness. An emergency head CT Scan showed a very large left-sided parieto-occipital hematoma with midline shift and left lateral ventricular hemorrhage as well as right-sided sylvian valley hemorrhage. She deteriorated neurologically and became progressively comatose with flat EEG. Family studies showed a FVII level of 95% in the mother and 75% in the father. DNA was extracted from the peripheral blood of the child and both parents and genetic studies were performed. The nine exons with boundaries of the proband's FVII gene were screened for mutations using direct sequencing. The child was found to be homozygous for a splice site mutation located at the invariant GT dinucleotide at the 5' donor splice site of intron 2: IVS2+1 ACGgt®ACGct. This mutation creates a DdeI restriction enzyme site (c/tnag) leading to an easily reading electrophoretic pattern of the digested products. It is often associated with severe clinical phenotypes such as intracranial hemorrhages. Both parents were found to be heterozygous. At her next pregnancy, amniocentesis was performed at 17 weeks and the DNA was analyzed for the mutation reported in exon 2 of the FVII gene and was found to possess the IVS2+1 (ACGgt®ACGct) mutation at the heterozygous state. These results demonstrate the reliability and convenience of the genotyping method for prenatal diagnosis of FVII deficiency.