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Fedota A.M

Abstract. Introduction. Spectrum and prevalence of monogenic hereditary diseases in Ukrainian population are well represented by many authors. Most diseases occur as a Ukrainian, and in other European populations, although their prevalence varies considerably. In Ukraine, describes not only pervasive, but also unique mutations, either directly or as predictors conditional on the development of hereditary pathology. High levels of inbreeding, especially in rural areas, causes an increase in the frequency of monogenic recessive diseases such as enzymopathies, severe dermatoses, different forms of hearing and vision loss, posing a serious threat to the genetic safety of the population. One of the possible ways of reducing the incidence of recessive disease is genetic counseling based on the calculation of the genetic risk of this pathology in a families. Genetic prediction with monogenic pathologies associated with a number of features: clinical polymorphism and genetic heterogeneity, possible incomplete penetrance and variable expressivity, age and gender and ethnic characteristics, the existence genocopies and phenocopies, and many others, which makes it necessary not only analysis of monogenic traits in each population, but also the inclusion of these features in the calculation of the quantities of the genetic risk of developing the disease, which is presented in this paper on the example of ichthyosis.

Materials and methods. Collection of genealogical information held by a single registration of a proband with the ethical requirements when working with a person in a Regional Clinical Skin and Venereal Diseases Dispensary №1 of Kharkiv. Determining the type of inheritance of the disease was conducted with specialists on the basis of the analysis of the results of clinical, genealogical, laboratory and literature (OMIM) database. The relative risk and confidence intervals were calculated.

Results of the study. To compile the genetic prognosis for monogenic diseases requires information on the prevalence of the analyzed forms of the disease in a population, genealogical information and the results of laboratory studies of the proband and, if necessary, his relatives. In the Kharkiv region frequency of ichthyosis simplex lies in the range from 1: 121 to 1: 21,018, on average - 1: 2557. Genotyping of ichthyosis patients and their relatives, from Kharkov region, for the transitions 1501C-to-T (R501X) and deletions 2282del4 in the FLG gene revealed heterozygotes, homozygotes and compounds both sexes.

No fundamental differences between the phenotypic expression, their location and severity, with mutations R501X and 2282del4 patients heterozygotes have been identified. The study showed that homozygous for mutation 2282del4 and compounds have more severe phenotype compared with patients-heterozygous for which the severity of the disease varies greatly. Penetrance of R501X mutations in FLG gene, according to our data, was 100%, although the small number of samples does not allow to consider the value unambiguous. Penetrance of 2282del4 mutations is 84,2%. These facts show the importance of calculating the forecast not only for each form of the disease, but also for each genotype, which will calculate a more accurate forecast for posterity. Example of calculation of the value of genetic risk. Analysis of genealogical information and clinical manifestations of the proband B., age 11, resident of Kharkiv region, evidence in favor of an autosomal dominant mode of inheritance of the disease and suggest ichthyosis simplex. Molecular genetic analysis of R501X and 2282del4 mutations in FLG gene identified 2282del4 in FLG gene in the heterozygous state. Genetic characteristics of the resulting analysis on population, family and individual levels, are used to develop the genetic prognosis of monogenic diseases, as illustrated in this paper on the example of ichthyosis. Patients with ichthyosis caused by a mutation 2282del4 in FLG gene, married to the patients of the same form of ichthyosis or carrier mutations in FLG, may have a sick child with a probability of 67% to 100% depending on the type of mutation and genotype of mating partner, regardless of the sex of the child. In the case of marriage with a healthy person and not carriers of the mutation in the FLG gene probability to development of ichthyosis for child - 67%.

Conclusion. The patients and their relatives, persons with an increased risk of ichthyosis, must obtain specific information about the nature and characteristics of ichthyosis, about development opportunities in other family members, and its primary prevention measures: how to resolve violations of hygienic behavior, rationalizing lifestyle (good nutrition, hardening of the body, occupational health and recreation, and so on), recommendations for a possible diagnosis of the disease in relatives at risk and psychological help.

Keywords: ichthyosis simplex, monogenic diseases, genetic risk.

Рецензент – проф. Дудченко М.О.

Стаття надійшла 11.09.2014 р.

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