A nonstop mutation in the factor (F)X gene of a severely haemorrhagic patient with complete absence of coagulation FX.

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 3'-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.

Natural Language Processing Based Instrument for Classification of Free Text Medical Records.

According to the Ministry of Labor, Health and Social Affairs of Georgia a new health management system has to be introduced in the nearest future. In this context arises the problem of structuring and classifying documents containing all the history of medical services provided. The present work introduces the instrument for classification of medical records based on the Georgian language. It is the first attempt of such classification of the Georgian language based medical records. On the whole 24.855 examination records have been studied. The documents were classified into three main groups (ultrasonography, endoscopy, and X-ray) and 13 subgroups using two well-known methods: Support Vector Machine (SVM) and K-Nearest Neighbor (KNN). The results obtained demonstrated that both machine learning methods performed successfully, with a little supremacy of SVM. In the process of classification a "shrink" method, based on features selection, was introduced and applied. At the first stage of classification the results of the "shrink" case were better; however, on the second stage of classification into subclasses 23% of all documents could not be linked to only one definite individual subclass (liver or binary system) due to common features characterizing these subclasses. The overall results of the study were successful.

A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels.

Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. Because less than 2.5% of the structural FVIII gene (F8) has been examined previously, we resequenced all known functional regions in 222 potentially distinct alleles from 137 unrelated nonhemophilic individuals representing 7 racial groups. Eighteen of the 47 variants identified, including 17 single-nucleotide polymorphisms (SNPs), were previously unknown. As the degree of linkage disequilibrium across F8 was weak overall, we used measured-genotype association analysis to evaluate the influence of each polymorphism on the FVIII:C levels in 398 subjects from 21 pedigrees known as the Genetic Analysis of Idiopathic Thrombophilia project (GAIT). Our results suggested that 92714C>G, a nonsynonymous SNP encoding the B-domain substitution D1241E, was significantly associated with FVIII:C level. After accounting for important covariates, including age and ABO genotype, the association persisted with each C-allele additively increasing the FVIII:C level by 14.3 IU dL(-1) (P = .016). Nevertheless, because the alleles of 56010G>A, a SNP within the 3' splice junction of intron 7, are strongly associated with 92714C>G in GAIT, additional studies are required to determine whether D1241E is itself a functional variant.