title: Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).
abstract: Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.
authors.affiliation: Laboratory of Haematology, University Hospital, Montpellier, France. m-giansily@chu.montpellier.fr
authors.forename: Muriel
authors.initials: M
authors.lastname: Giansily-Blaizot
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Martinez
authors.forename: Marie-Elisabeth
authors.initials: ME
authors.lastname: Briquel
authors.forename: Roseline
authors.initials: R
authors.lastname: d'Oiron
authors.forename: Emmanuel
authors.initials: E
authors.lastname: De Maistre
authors.forename: Serge
authors.initials: S
authors.lastname: Epelbaum
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Schved
mesh_terms: D001483:Base Sequence; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000235:genetics; D018389:Codon, Nonsense; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D017354:Point Mutation
chemical_list: D018389:Codon, Nonsense; D005167:Factor VII; D004247:DNA