A first genetically proven case of factor VII deficiency in Latvian family

Introduction: Factor VII (FVII) deficiency is the most common rareinherited autosomal recessive bleeding disorders with different clin-ical manifestations. Only small amounts of FVIIa are needed totrigger coagulation. FVII deficiency is characterised by a wide spec-trum of clinical phenotypes from asymptomatic condition to severelife-threatening bleedings.Methods: F7 gene was sequenced by private laboratory using theIllumina’s sequencing-by-synthesis method with paired-end sequenc-ing. This test targeted protein-coding exons, exon-intron bound-aries (± 20 bps) and selected non-coding, deep intronic variants in themother and daughter.Results: We started genetic investigation in a 3-month-old child dueto mother’s FVII deficiency diagnosed during pregnancy. During preg-nancy the mother complained about minimal bleeding from mamillabruise, was diagnosed with FVII 29%, received replacement ther-apy with FVII peripartum. Before pregnancy the patient had nosebleedings, minor bruising, severe menstrual bleeding, bleeding afterapendectomy and during ectopic pregnancy in the age of 21 years.Diagnosis was established during pregnancy in the age of 23 years.The child was born by caesarean section due to gluteal position of foe-tus, no bleedings during perinatal period were noticed. In the age of3 months skin haemorrhages were noticed, bleeding tests were per-formed, prolonged prothrombin time was detected, the FVIIc was 34%.Clinical manifestations during childhood were mild, more prominentbleedings were detected during dental manipulations. Until age of 6years only one hospitalisation occurred due to head trauma with largefrontal haematoma, no intracranial haemorrhage was detected. Untilage of 6.5 years the child received only few FVII injections DNA diagnostics identified homozygous pathogenic variantNM_000131.4 c.1061C > T, p.(Ala354Val), alias A294V, in F7 gene inthe mother, and heterozygous variant c.1061C > T, p.(Ala354Val) inthe daughter.Discussion/Conclusion: Variant NM_000131.4 c.1061C > T,p.(Ala354Val) in F7 gene has previously been described as pathogenicin Factor VII Gene variant database. The highest allelic frequencyrecorded in Estonian population is 0.23% (gnomAd). All in silicotools predict damaging effect, CADD score is 23. Decreased FVIIcwas observed (PMID: 15735798). The precise frequency in Latvianpopulation is unknown, needs additional investigation.Disclosure of Interest: None declared.