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A severe neonatal presentation of factor II deficiency
Author(s) -
Pasmant Eric,
Dumont Bénédicte,
Lacapere JeanJacques,
Dautzenberg MarieDominique,
Bezeaud Annie
Publication year - 2011
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2011.01670.x
Subject(s) - missense mutation , hypoprothrombinemia , medicine , heterozygote advantage , consanguinity , gastroenterology , pediatrics , intracranial bleeding , kringle domain , compound heterozygosity , mutation , endocrinology , genetics , gene , biology , allele , vitamin k , anticoagulant , recombinant dna
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.