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Characterization of two novel splice site mutations in human factor VII gene causing severe plasma factor VII
Keren Borensztajn1, Ouerdia Chafa, Martine Alhenc-Gelas
1INSERM U428, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Insights
Severe factor VII deficiency in two Algerian patients was linked to novel genetic mutations affecting mRNA processing. These findings shed light on the molecular basis of this rare bleeding disorder.
Area of Science:
- Genetics
- Molecular Biology
- Hematology
Background:
- Factor VII (FVII) deficiency is a rare inherited bleeding disorder.
- Understanding the molecular basis of severe FVII deficiency is crucial for diagnosis and treatment.
Observation:
- Two Algerian patients with severe FVII deficiency were studied.
- One patient had a homozygous 7-bp deletion and a mitochondrial insertion at the IVS 4 acceptor splice site.
- The second patient had a homozygous transversion at the IVS 7 donor splice site and a missense mutation in exon 8.
Findings:
- Novel genetic mutations were identified in both patients.
- The identified mutations involve splice site abnormalities.
- These mutations likely impair messenger RNA (mRNA) processing, leading to severe FVII deficiency.
Implications:
- The study identified three previously unreported genetic lesions causing FVII deficiency.
- These findings expand the known spectrum of mutations associated with FVII deficiency.
- Understanding these novel mutations can improve genetic counseling and diagnostic approaches for patients with bleeding disorders.
Abstract:
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.