title: A severe neonatal presentation of factor II deficiency.
abstract: Prothrombin deficiency is an autosomal recessive disorder associated with moderate or severe bleeding tendency. In this study, a three-month-old boy with non-consanguineous parents was referred for convulsions because of intracerebral hemorrhage. Standard coagulation tests revealed that the patient's plasma prothrombin activity was 12%, while his father's and mother's levels were 55% and 70%, respectively. Analysis of the prothrombin gene revealed that this patient is a compound heterozygote for two missense mutations: one maternally inherited point mutation in the propeptide (p.Arg4Gln) and one paternally inherited mutation in the kringle-2 (p.Arg220Pro) domain. Structural analysis was performed and confirmed that the resulting mutations were inferred to respectively affect the cleavage of the propeptide from the Gla domain, and the stability of the kringle-2 domain, both resulting in a severe hypoprothrombinemia. In unusually bleeding newborn of non-consanguineous parents, rare severe homozygous bleeding disorders need to be considered to facilitate early diagnosis and treatment.
authors.affiliation: Département d'Hématologie et immunologie, Hôpital Beaujon, AP-HP, 100 boulevard du Général Leclerc, Clichy, France. eric.pasmant@gmail.com
authors.forename: Eric
authors.initials: E
authors.lastname: Pasmant
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dumont
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lacapere
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Dautzenberg
authors.forename: Annie
authors.initials: A
authors.lastname: Bezeaud
mesh_terms: D006801:Humans; D007020:Hypoprothrombinemias / Q000151:congenital / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D007223:Infant; D008297:Male; D017354:Point Mutation; D011516:Prothrombin / Q000235:genetics
chemical_list: D011516:Prothrombin