[Psychosocial factors associated with genetic testing for certain hereditary types of neoplasms]. / Psychosociální faktory spojené s genetickým testováním nekterých dedicne podmínených nádorových onemocnení.

Mutations in predisposing genes for some of the hereditary forms of cancer exhibit autosomal dominant mode of inheritance. Introduction of genetic tests for these mutations to the clinical practice initiated studies focused on the psychosocial factors associated with genetic testing. Undergoing the genetic testing is a stressful experience for both the healthy individuals in risk and the patients already affected with cancer. The psychosocial characteristics of the tested individual influence not only the psychological functioning during the testing but also the acceptance of the test, and generally his life style and health practices. Psychological support during the genetic testing process is mostly provided by the genetic counsellor. The findings of psychosocial studies might be therefore helpful for the focusing of the genetic consultation, and fulfilling the client needs and expectations towards testing. Factors of motivation, psychological state, influence of family situation and support, and optionally the involvement of a psychologist into the process of genetic testing are observed.

Four novel mutations of the PKD2 gene in Czech families with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease caused by mutations in at least three different loci. Mutations in the PKD2 gene are responsible for approximately 15% of the cases of the disease. We have screened 14 Czech families for mutation in the PKD2 gene. Clear evidence against linkage to the PKD1 gene was established by CA-repeat markers in five families. The disease could be linked to both genes according to linkage analysis in nine families but we have chosen these families because of the mild clinical course. An affected member from each family was analyzed by heteroduplex analysis (HA) and single strand conformation polymorphism (SSCP) for all 15 coding regions. Samples exhibiting shifted bands on HA or SSCP gels were sequenced. We detected five mutations (four new, and one which was previously described) and two polymorphisms. The four new mutations include one insertion, one deletion, one substitution (leading to premature translation stop), one amino acid substitution. Our results confirm that different point or small changes distributed throughout the PKD2 gene without clustering are responsible for the disease.

[Human cloning--a controversial issue of today]. / Klonování cloveka--kontroverzní téma dneska.

Human cloning has been the subject of much debate both in the scientific community and the public during the past year. The world-wide variations in opinion among scientists, ethicists and executives is discussed. The cloning debate is a prerequisite for socially responsible decision-making.

Huntington's disease: the relationship between clinical signs, CAG repeats and the atrophy of the caudate nucleus in CT scans.

We compared clinical data from 45 patients with Huntington's Disease (HD) with CAG triplet repeats and the planimetric measurement of the caudate nucleus head area (CNHA) in CT scans. The mean age of patients was 50.4 yrs (SD +/- 10.2), the mean duration of HD 7.4 yrs (4.6), the mean age at the onset of HD 43.1 yrs (11.1). HD started with motor symptoms in 28 patients, with psychiatric symptoms in 14 patients, the history was unknown in 3 patients. The paternal transmission was observed in 29 patients, the maternal one in 12 patients, unknown in 4 patients. The mean number of CAG repeats was 46.6 (6.1). The mean CNHA was 0.4 cm2 (0.1). We found statistically significant reversed correlation between CAG repeats and the age at the onset of HD (p < 0.0001, r -0.6). The earlier onset of HD in patients with the paternal transmission compared to the maternal one was found statistically significant (p < 0.05). This phenomenon was not related to the larger number of CAG triplets in patients with the paternal transmission. No differences either of the age at the onset of HD or numbers of CAG repeats were found between subgroups of HD patients starting with motor or psychiatric symptoms. We also observed the significant reversed correlation between the duration of HD and CNHA measurement (p < 0.001, r -0.5). Even in the earliest stage of HD patients showed the marked atrophy of CNHA.

[Cleft lip and palate--prenatal diagnosis and counseling]. / Rozstep rtu a patra--prenatální diagnostika a poradenství.

The most frequent congenital developmental defect in the orofacial region are, no doubt, facial clefts which are a serious stress for health professionals and the population. Depending on the type of cleft, the prevalence is between 1 : 1000-2800 births. According to contemporary views in the etiology of orofacial clefts participate genetic as well as environmental factors. That means that specific genetic factors create a certain "sensitivity" for specific factors of the external environment which act as a trigger mechanism and combined they produce the cleft. Cleft lip can be diagnosed already during the 13th week of gestation, while a cleft palate is not necessarily apparent till after the 18th week of gestation as the maxilla is in the process of joining. Presentation of the foetal face and its profile is thus important in particular during the second trimester of gestation and should be part of ultrasonographic screening between the 18th and 20th week of gestation. As more than 8% of facial clefts are associated with chromosomal abnormalities, in all affected foetuses karyotyping is done. The prognosis of satisfactory cosmetic and functional repair in cleft lip and in cleft lip and palate is favourable. In case of associated malformations all depends on the type and severity of these associated defects or on the diagnosis of the syndrome. If median clefts are extensive or associated with cerebral anomalies, the prognosis is as a rule poor. Prenatal diagnosis and management of defects of the orofacial area calls for collaboration of the obstetrician, neonatologist and plastic surgeon already in the stage when the defect is detected to give the expectant mother an opportunity to obtain accurate and unbiased information on possible treatment and prognosis for the foetus.

DNA diagnosis and clinical manifestations of autosomal dominant polycystic kidney disease.

At least 2 genes, detectable by DNA methods, encode autosomal dominant polycystic kidney disease (ADPKD), which remains the most frequent and serious hereditary renal disease. PKD1 gene, localized on chromosome 16, responds for the clinical course in the majority of ADPKD patients, whereas PKD2 gene, localized on chromosome 4, is responsible for less than 10-15% of cases, with presumed milder phenotypic manifestations. To start the clinical and genetic correlation in patients with different genotypes (PKD1 vs. PKD2) in the Czech population, a pilot group of 88 patients with ADPKD was analysed. Families with PKD1 (n = 44) represented 95.6% and families with PKD2 (n = 2) 4.4% of all families investigated (n = 46). Our clinical analysis, yet based only on a limited number of PKD2 subjects, does not definitely support the concept of a milder phenotype and prognosis in PKD2 versus PKD1 patients, in terms of mean age of diagnosis (29 vs. 29 years), mean age at onset of arterial hypertension (33 vs. 33 years), more favourable renal function or ultrasound findings.

[Autosomal dominant hereditary polycystic kidney disease]. / Autosomálne dominantne dedicná polycystická choroba ledvin.

BACKGROUND: Molecular genetics are a fundamental turning point in the approach to autosomal dominant hereditary renal polycystosis of adults (ADPKD). DNA analysis makes diagnosis possible at in any ontogenic period, i.e. also during the prenatal period. The objective of the present study was to test the presymptomatic DNA diagnosis in a major group of patients with ADPKD and the possibility to detect the disease in the initial stage and influence its development by early treatment and advise the patients on parenthood. METHODS AND RESULTS: In 1990-1994 the authors contacted 157 patients with polycystic kidney disease, adult type (ADPKD). 87 families were examined by Southern's RFLP method (gene PKD1, 16p13.3, standard probe 3'HVR and restrictase Pvu II). Of 493 members of these families only 25 (5.1%) refused to be examined. So far 378 examinations were completed, 90 proceed. In 40 of 132 examined subjects with the risk of ADPKD transmission of the gene was proved. Of four examinations of the foetus with the risk of ADPKD twice transmission of the gene was proved and the pregnancy was terminated. In three families with three or more members suffering from ADPKD in some there was not agreement between the result of linkage analysis of DNA and the clinical finding. The authors analyzed whether the cause is recombination or ADKPD conditioned by mutation of gene PKD2 (4p13-23). Linkage analysis remains in ADPKD the basic examination as the sequence of gene PKD1 is not yet completed. Discovery of gene PKD2 the mutations of which condition as many as 15% of all cases of ADPKD has an impact on the evaluation of linkage analysis. The reliability of prediction rises with the number of examined subjects in the family. The examination revealed that patients are willing to have DNA examinations (as many as 98%); despite this the number of examined subjects is only a small fraction of the anticipated 10,000 people in the Czech Republic suffering from ADPKD: CONCLUSIONS: DNA analysis in patients with autosomal dominant polycystic kidney disease is the most important examination for its diagnosis. It makes the diagnosis possible in all stages of ontogenesis, incl. prenatal diagnosis. It is a highly valid parameter when these patients decide on parenthood. It makes early treatment possible which can influence the development of the disease and its complications.

[The attitude of family members with polycystic kidney disease to the disease and presymptomatic testing]. / Postoje clenu rodin s polycystickou chorobou ledvin k onemocnení a presymptomatickým testum.

BACKGROUND: The application of presymptomatic diagnosis of polycystic kidney disease (PKD) relies on satisfactory collaboration between the affected families and the team of health workers. The objective of the present study was to assess the initial level of knowledge of the disease and its hereditary character, the attitudes of families with PKD to presymptomatic and prenatal testing focused on methods of molecular genetics as well as attitudes to induced abortion if the gene of PKD is detected in the foetus. METHODS AND RESULTS: In a group of 104 subjects who had genetic examinations on account of familial PKD by means of questionnaires knowledge of the diagnosis, clinical and genetic prognosis and attitudes to presymptomatic and prenatal genetic tests were investigated. About 75% of the members of the group had adequate knowledge of the name of the disease and description of the clinical picture, 96.1% were informed on the hereditary character of the disease but only 1.9% knew details about the heredity. The scope of genetic risk was mentioned by some 30%, 51% were unable to express their opinion on the risk. A positive attitude to testing for the presence of the PKD gene was recorded in almost 100% if they themselves were concerned, 94% when their offspring under age was concerned but only 19.2% when the foetus was concerned. Only 5.3% of the respondents would agree with induced abortion in case of positive prenatal evidence of the PKD gene in the foetus and a few more respondents (14%) were opposed to abortion and some 80% were unable or unwilling to express their opinion. CONCLUSIONS: In members of families with PKD an important role is played by knowledge of clinical and genetic aspects of the disease. Genetic counselling must be part of comprehensive care and should always precede indication of molecular genetic methods (DNA analyses).

[DNA diagnosis in families with autosomal dominant hereditary polycystic kidney disease]. / Problémy DNA diagnostiky v rodinách s autosomálne dominantne dedicnou polycystickou chorobou ledvin.

In 1990-1992 110 patients with polycystic kidney disease adult type (ADPKD) were contacted. Forty-nine families were examined by Southern's RFLP method (standard probe 3'HVR and Pvu II restrictase). Of 424 members of these families only 25 (5.9%) refused the examination. So far 337 examinations were completed, 62 are under way. In 32 cases of 109 subjects at risk of 50% ADPKD the affection was proved with a probability higher than 95%, in 77 subjects (and 6 subjects with a 25% risk) were eliminated with an equal probability. In two families successful prenatal examinations of the foetus were accomplished. Evaluation of attitudes to DNA diagnostics revealed in our patients a greater willingness to attend postnatal examinations (up to 98%) and a smaller willingness to have prenatal examinations (21%), as compared with data published abroad.

[16q+ partial trisomy in a 7-day-old surviving neonate]. / Parciální trisomie 16q+ u 7 dní zijícího novorozence.

A proband with a complex malformation; chromosomal examination revealed partial trisomy for the long arms of chromosome 16. The child's father, the father's twin brother and the father's mother are carriers of the balanced translocation 14/16.

[Genetic consultation in psychotic disorders]. / Genetická konzultace u psychotických onemocnení.

The author gives an account of the problem of psychotic diseases in the practice of a genetic department. She mentions the specificity of decision taking on the reproduction in psychotic subjects, where in addition to the empirical risk of affection of the offspring and the possible teratogenic effect of medication, the load associated with the disease from the medical and socio-economical aspect must be considered. These factors are subject to the subjective interpretation by the family. The task of the geneticist is to help a rational solution of the situation in close cooperation with the psychiatrist.