RESUMEN
: Congenital factor X deficiency is a rare coagulation defect characterized by variable bleeding tendency. The aim of the study was to give a first insight of F10 gene mutations in Pakistani probands. Direct sequencing and/or next-generation sequencing was performed on the coding regions, boundaries and 5' and 3' untranslated regions of the F10 gene in five severe factor X-deficient patients from Pakistan. All patients were born from consanguineous marriages and displayed FX:C levels below 2%. Sequencing revealed five different substitutions, including three previously reported p.Ala15Asp, p.Gly406Ser, and p.Gly420Arg missense variants, and also two novel variants: p.Cys57Arg and p.Gln175*. Though one genotype could not be characterized, we were able to confirm the inherited nature of the defect using familial studies. As the copy number variations were ruled out, we hypothesized the presence of deep intronic mutants that might have escaped detection from sequencing or abnormalities in epigenetic regulation. Three patients presented with severe clinical symptoms, in the early days of life, whereas two presented only with trauma-provoked bleeds and bruises later in life. Those patients with milder forms bore the p.Gly406Ser at the homozygous state and F10 unknown alleles, respectively. F10 mutation spectrum in Pakistan is heterogeneous as seen in other populations. Identification of the F10 mutations is important for genetic counseling and prenatal diagnosis in subsequent pregnancies.
Asunto(s)
Deficiencia del Factor X/genética , Factor X/genética , Genotipo , Mutación , Sustitución de Aminoácidos , Hemorragia/genética , Humanos , Mutación/genética , Pakistán , Análisis de Secuencia de ADNRESUMEN
Using survey data from the 2009 wave of the European Union Statistics on Income and Living Conditions, this study examines the determinants of unmet needs for medical and dental care in European countries. Special emphasis is put on the impact of health system characteristics. Four factors are taken into account: the density of doctors or dentists, the rules governing access to practitioners, the method of paying primary care physicians, and the amount of out-of-pocket payments. The analysis is carried out using multilevel logistic regression models. Separate regressions are estimated for medical and dental services. The dependent variable is whether respondents reported that, at least once in the last 12 months, they needed care but did not receive it. The estimation results show that the probability of experiencing unmet medical or dental needs varies noticeably across countries. This inter-country variability seems to be partly explained by the differences in the financing of health care. Indeed, a positive link is found between the share of households' out-of-pocket payments in total health expenditure and the probability of unmet needs. The other contextual factors do not seem to play a significant role.