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Objective: In the Czech Republic, over 97% of all pregnant women undergo some type of antenatal screening for Down's syndrome. In about 95% of cases with a confirmed fetal chromosomal abnormality, the pregnancy is terminated. The most commonly used test is the first trimester combined test. We investigated the impact of implementing an integrated sequential test to improve the detection of Down's syndrome pregnancies., Methods: Data on the incidence of congenital defects, number of births, and affected pregnancies terminated are recorded in the National Registry of Congenital Anomalies. Anonymous data on cases of Down's syndrome diagnosed antenatally or postnatally between 2010 and 2015 in one of the large antenatal care centers were analyzed., Results: There were 600 diagnoses of Down's syndrome (5.7 per 1000 births), 90% of which were made antenatally. Of antenatally detected cases, 80% were indicated for diagnostic procedure by multimarker screening results. In the multimarker screen positive group, 75% cases were first trimester positive and 25% second trimester positive (most of these had positive integrated test results). Among Down's syndrome cases indicated for antenatal diagnosis by multimarker screening results 6.25% (n = 26) were first trimester negative, and became positive after integration with the second trimester screening results., Conclusions: Results from five major Czech antenatal centers confirm that an integrated sequential test would detect 80-85% of Down's syndrome fetuses in the first trimester and at least an extra 5-10% of Down's syndrome pregnancies in the second trimester of pregnancy. These are important data that should be considered in implementing the national antenatal screening program.

The SPAST gene has a major role in hereditary spastic paraplegias (HSPs). This is the first report mapping characteristics of the SPAST gene in a large cohort of Czech HSP patients. All 17 coding exons of the SPAST gene were Sanger sequenced in 327 patients from 263 independent families with suspected uncomplicated HSP. The selected 126 independent patients, without mutation in the SPAST gene after Sanger sequencing, were subsequently tested by Multiplex Ligation-dependent Probe Amplification (MLPA) assay for large deletions or copy number variations affecting the SPAST gene. Among the 263 independent patients, 35 different, small mutations in 44 patients were found. Twenty-one mutations are novel with the majority of frameshift mutations. Seven mutations were found in more than one family. The age at onset ranged between preschool childhood and the fifth decade with inter- and intra-familiar differences. SPAST small mutations were detected in 16.7% (44/263) of independent tested patients. Mutations in the SPAST gene were found more frequently in familial cases (with affected relatives). Mutation were found in 31.9% (29/91 familial tested) in the familial patient group, whereas in the sporadic patient group, mutations were found in only 4.7% of cases (5/106 sporadic cases). Among SPAST-positive patients, 65.9% (29/44) were familial but only 11.4% (5/44) were sporadic. MLPA testing revealed four large deletions in four independent patients, all in familial-positive cases. Mutations in the SPAST gene are 5.8 × more frequent in familial than in sporadic cases. Large deletions were found only in familial patients. Diagnostic testing of the SPAST gene is useful only in positive family history patients not in sporadic cases.

We present the results from the largest clinical application of QF-PCR for antenatal rapid aneuploidy detection (RAD) in routine prenatal diagnosis in the Czech Republic. QF-PCR was performed in addition to karyotyping (dual testing) in two settings: the first was a single multiplex reaction testing only trisomy 21 and amelogenin X/Y alleles in the second trimester screened positive cases (T21 test), and the second setting consisted of two multiplexes (2M test) for common aneuploidies (13, 18, 21, X and Y) in cases with other RAD indications such as ultrasound findings, late booking or maternal anxiety. Dual testing was performed in 6349/12,778 (49.7%) of prenatal samples using either T21 or 2M test between 2002 and 2007. The clinical acceptability of our dual testing policy, methodological efficiency of RAD and residual risks of other chromosomal aberrations (CHAs) were evaluated. QF-PCR detected 92% (175/190) of significant CHAs. The 2M test identified 93.5% and the T21 test identified 87.5% of the significant CHAs with complete specificity. The residual risk of significant CHA was 1/231 in the 2M test and 1/565 in the T21 test. If RAD for all common aneuploidies is used as the sole prenatal diagnosis method, the odds of missing a CHA of any type are 1:90 and the odds of missing significant CHA with no ultrasound findings are 1:1513. If prenatal karyotyping were used as an additional procedure to RAD in cases only with ultrasound findings, 186/190 (97.8%) of the significant CHAs would be detected when 15.7% cases were karyotyped, according to our data. We consider RAD directed towards trisomy 21 alone (our T21 test) as an economically and clinically acceptable part of second trimester screening for Down syndrome. Both RAD tests allow fast alleviation of maternal anxiety with low residual risk when the test results are negative, and allow fast decision making if the results are positive. However, replacement of dual testing with only the RAD procedure in specific indications accepted in some countries (Great Britain) remains in the Czech Republic a theme for debate.

Objectives: Detection of free plasma metanephrines seems to be the most exact method for biochemical diagnosis of pheochromocytoma, but their diagnostic efficacy in the common low-risk clinical settings is debated., Methods: A cross-sectional multicentre study including 1260 subjects assessed the diagnostic efficacy of free plasma metanephrine and normetanephrine in low-risk patients screened for resistant or markedly accelerated hypertension, paroxysmal hypertension, 'flushes' and, in a small proportion, for adrenal incidentaloma or genetic predisposition to pheochromocytoma., Results: Pheochromocytoma was identified and verified by histology in 25 subjects (2%), with the diagnosis not confirmed by long-term follow-up or use of imaging techniques in the remaining 1235 individuals. The combined assay of free plasma metanephrines was a highly sensitive (100%) and specific (96.7%) measure, yielding a negative predictive value of 100%., Conclusion: The satisfactory diagnostic efficacy of free plasma metanephrines allows their use as a single screening test in cases of suspected pheochromocytoma in the population with a low pretest probability.

Introduction: Leptin is a protein, determined by the ob-gene which influences in a fundamental way the energy metabolism of the organism. A significant effect of leptin on the haematopoietic, immunological and endocrinological system cannot be ruled out nor its effect on the course of pregnancy and maturation of the organism. In humans leptinaemia correlates with the amount of subcutaneous fat which is due to a receptor or post-receptor disorder, obese subjects suffer frequently from hyperleptinaemia., Objective: To assess the mean leptinaemia of the general population, seek relations between leptinaemia and anthropological indicators and age., Methods: Using the method of random sampling the authors examined a group of 538 probands (252 males, 286 females) incl. 12% healthy students of the Faculty of Physical Culture in Olomouc, 37% subjects without acute or chronic complications feeling in good health and 37% patients of the metabolic and diabetological ambulance of the hospital in Sternberk. In each patient a detailed case-history was recorded, an anthropological examination was made and a venous blood sample was taken for leptin analysis (serum, ELISA-sandwich method of BIOVENDOR Co.), Results: Spectrum of patients, whose condition and age distribution in our group corresponded to the general population of the Czech Republic. The mean age of the probands was 51 years (18 to 82 years), the examined group can be characterized as subjects lacking signs of obesity. Leptinaemia was on average about 10 ng/ml (minimum 0, maximum 97.9 ng/ml), whereby men had values round 6 and women round 14 ng/ml (women had also a greater adipose tissue mass). Non-obese subjects (BMI<26) had a mean leptinaemia of 5 (women cca 6, men cca 2 ng/ml), obese subjects (BMI>30) have a leptinaemia of cca 19 ng/ml (women about 26, men about 13 ng/ml). With advancing age the leptinaemia in adults rises up to the age of 70, in subjects above 70 years it does not change (in women it declines significantly). The dynamics of leptinaemia imitate the changes of BMI and percentage of adipose tissue (in men also a rise in WHR). Leptinaemia is associated with the BMI (correlation coefficient 0.55), with the percentage of body fat (correlation coefficient 0.75), and in men with the WHR (correlation coefficient 0.82). The association between ageand leptinaemia is only indicated (correlation coefficient 0.29) and is not very close. According to the authors results subcutaneous body fat is responsible for cca 60% of the variability of leptinaemia (in women as much as 74%), BMI for 23%, age and sex for cca 9% of the vriability of leptinaemia. In men the WHR is responsible for 66% of the variability of leptinaemia. With an increase of subcutaneous adipose tissue by 1% the leptinaemia increases by some 0.54 ng/ml (in men by 0.22 ng/ml, in women by 0.84 ng/ml), with increasing BMI leptinaemia rises by 0.44 ng/ml/u (in men by 1.3 ng/ml, in women by 1.72 ng/ml), with advancing age leptin rises by 0.24 ng/ml/year (in men by 0.16 ng/ml, in women by 0.28 ng/ml), changes of leptinaemia imitate changes of BMI and the percentage of body fat. With increasing WHR in men the leptinaemia rises by 2.6 ng/ml/0.1 WHR., Conclusion: Standards of leptinaemia for the general population of the Czech Republic were elaborated. Leptinaemia correlates most closely of all anthropometric indicators with subcutaneous fat and in men with the WHR index. With advancing age between 20 and 70 years leptunaemia rises and then decliunes insignificantly (in women the changes are however significant). The primary cause of the mentioned differencesare probably changes of the bodily constitution.