
<ArticleTitle><prot>Severe factor VII</prot> deficiency with recurrent intracranial haemorrhages owing to double heterozygosity for a splice site mutation of an <prot>IVS4</prot> and a novel nonsense mutation in exon 8 (Gln211--Term).</ArticleTitle>
<AbstractText>Genetic analysis of a 10-month-old Japanese baby boy with recurrent intrathoracic bleeding, cerebral haemorrhages and gastrointestinal bleeding secondary to <prot>severe factor VII</prot> (<prot>FVII</prot>) deficiency revealed evidence of two distinct mutations of <prot>FVII</prot>: a splice site mutation of G--A at nucleotide 6071 in the <prot>IVS4</prot> splice site and a novel nonsense mutation (Gln211--Term) in exon 8. His bleeding was difficult to control without prophylactic infusion of <prot>FVII</prot>. We detected a heterozygous splice site mutation of the <prot>IVS4</prot> in his mother and a heterozygous nonsense mutation in exon 8 (Gln211--Term) in his father. The parents' <prot>FVII</prot> levels are both 50% of normal controls. The <prot>FVII</prot>:C in plasma from the proband was &#60; 1.5% of normal controls. <prot>FVII</prot>:antigen (Ag) was &#60; 1% of normal controls, using a monoclonal antibody (mAb) <prot>hVII-B101/1</prot> that specifically reacts with <prot>FVII</prot> <prot>epidermal growth factor 1</prot> (<prot>EGF-1</prot>), and 5% of normal controls, using a rabbit polyclonal antibody against human <prot>FVII</prot>. After immunoadsorption with mAb <prot>hVII-B101/B1</prot>-Sepharose 4B, <prot>FVII</prot> levels of both the proband and his mother were 5% of normal controls; after immunoadsorption the <prot>FVII</prot> levels of normal subjects were &#60; 1%. We hypothesize that secretion of a small amount of dysfunctional <prot>FVII</prot> lacking <prot>EGF-1</prot> into the circulation accounts for this observation.</AbstractText>
