Characterization of two novel splice site mutations in human factor VII gene causing severe plasma factor VII deficiency and bleeding diathesis.
The molecular basis of severe type I factor (F)VII deficiency was investigated in two Algerian patients. One patient, a 13-year-old-girl who has suffered from severe bleeding since birth, was homozygous for a 7-bp deletion (nt 7774-7780) and a 251-bp insertion (nt 7773-7781) of mitochondrial origin, in IVS 4 acceptor splice site. The other patient, an infant who died from massive intracranial haemorrhage, was homozygous for a transversion in the IVS 7 donor splice site (T9726+2-->G) and a missense mutation in exon 8 (G10588-->A; Arg224-->Gln). In both cases, the deleterious mutations are probably the splice site junction abnormalities impairing mRNA processing. These three lesions have not yet been reported.
Borensztajn
Keren
K
INSERM U428, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Chafa
Ouerdia
O
Alhenc-Gelas
Martine
M
Salha
Siham
S
Reghis
Abderrezak
A
Fischer
Anne-Marie
AM
Tapon-Bretaudière
Jacqueline
J
D000293:Adolescent; D000462:Algeria; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense
D005167:Factor VII