Abstract
We identified a previously unknown mutation by sequencing the factor (F)X gene in a severely haemorrhagic 14-year-old male African-American individual with undetectable plasma FX-activity and -antigen levels. This mutation, called F10-Augusta, was homozygote and is a combination of an 8bp insertion in flanking 3′-genomic-DNA and a 5bp terminal exon-8 deletion involving codons 437 and 438. Sequencing of RT-PCR and T-RACE products showed that the F10-Augusta transcript is normally processed but lacks an in-frame stop codon. An allele specific 3′-RACE-based RFLP assay demonstrated that the steady-state concentration of the mutant transcript was markedly lower than that of the wild-type message in total-RNA samples from the patient's unaffected heterozygous parents. The recently discovered nonstop decay mechanism, a component pathway of the mRNA surveillance system, is a possible explanation for the reduced concentration of the mutant FX transcript.This is the first report implying such a mechanism in the pathogenesis of inherited bleeding disorders.
Original language | English (US) |
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Pages (from-to) | 1165-1169 |
Number of pages | 5 |
Journal | Thrombosis and Haemostasis |
Volume | 98 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2007 |
Keywords
- Autosomal recessive
- Congenital bleeding disorder
- F10-Augusta
- mRNA surveillance
ASJC Scopus subject areas
- Hematology