Most patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS-E) uses combination of absolute lymphocyte count (ALC) >15 × 109 /l, palpable lymphadenopathy, and unmutated immunoglobulin heavy-chain variable-region (IGHV) gene to predict the time to first-line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5-year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS-E score using an unselected, consecutive group of 130 Binet A patients. The 5-year TTFT was 11%, 36%, and 78% (C-statistic 0·74). Furthermore, we propose an alternative system (AIPS-E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5-year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5-year TTFT was 16%, 37%, and 80% (C-statistic 0·74). In conclusion, we have successfully validated the IPS-E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS-E, combining IGHV, fluorescence in situ hybridisation, and ALC.

• MeSH
• Time-to-Treatment statistics & numerical data   MeSH
• Chromosome Aberrations statistics & numerical data   MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell blood   diagnosis   mortality   pathology   MeSH
• Genes, Immunoglobulin Heavy Chain genetics   MeSH
• In Situ Hybridization, Fluorescence methods   MeSH
• Cohort Studies MeSH
• Humans MeSH
• Lymphadenopathy diagnosis   MeSH
• Palpation methods   MeSH
• Lymphocyte Count methods   MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Risk Factors MeSH
• Aged MeSH
• Neoplasm Staging methods   MeSH
• Research Design trends   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

Úvod: Využití biochemických markerů je nedílnou součástí screeningových vyšetření zaměřených na hodnocení rizika chromozomových aberací v rámci péče o těhotnou ženu. Práce blíže shrnuje vývoj a úspěšnost těchto metod v České republice. Metodika: Retrospektivní epidemiologická studie z dat Národního registru vrozených vad České republiky, vedeného v Ústavu zdravotnických informací a statistiky. Podrobnější informace o prenatálně diagnostikovaných případech jsou zjišťovány aktivně pod záštitou Společnosti lékařské genetiky a genomiky ČLS JEP. V práci je analyzována prenatální diagnostika chromozomových aberací (diagnózy Q90Q99) v období 1994–2017.Výsledky: V roce 2017 byl biochemický, kombinovaný, příp. integrovaný screeningový test indikací k úspěšné prenatální diagnostice Downova syndromu v 92,5 % případů, zatímco na začátku sledovaného období to bylo pouze 13,46 %. Ve sledovaném období výrazně poklesla četnost Downova syndromu u narozených dětí (ze 7,79 na 10 000 živě narozených v roce 1994 na 3,48 na 10 000 živě narozených v roce 2017). Průměrný týden těhotenství při pozitivní prenatální diagnostice Downova syndromu poklesl z hodnoty 20,33 v roce 1994 na 13,97 v roce 2017. Diskuze: V posledních 20 letech prodělal prenatální screening chromozomových aberací v České republice výrazné změny. V rámci této epidemiologické retrospektivní studie prezentujeme vliv samostatného kombinovaného prvotrimestrálního screeningu jako součásti integrovaného testu na zvýšení prenatální detekce Downova syndromu a na časnější a efektivnější prenatální diagnostiku s nižší spotřebou výkonů invazivní prenatální diagnostiky.

Introduction: Analysis of biochemical marker is an important part of the prenatal screening examinations – calculating the risk of chromosomal aberrations of the foetus. The aim of this study is to evaluate the effectiveness of these methods in the Czech Republic. Methods: We present a retrospective epidemiological study using the data from the National registry of congenital anomalies, which is run by the institute of Health information and statistics of the Czech Republic. Additional information on prenatally diagnosed cases are obtained actively under the patronage of Society of Medical genetics and genomics of the Czech Medical Association. We analyzed the prenatal diagnostics of chromosomal aberrations (codes Q90Q99) during 1994–2017 time period. Results: In 2017 the biochemical (combined, or integrated) screening test was the referral for (successful) prenatal diagnosis of Down syndrome in 92.5% of cases, while at the beginning of the selected time period it was only in 13.46% of cases. During the selected time period – the incidence of Down syndrome in live births decreased significantly (from 7.79 per 10 000 live births in 1994 to 3.48 per 10 000 live births in 2017). The average week of gestation at the positive prenatal diagnosis of Down syndrome decreased from 20.33 in 1994 to 13.97 in 2017.Discussion: During last twenty years the effectiveness of prenatal screening of chromosomal aberrations in the Czech Republic increased significantly. In our retrospective epidemiological study, we observed the effect of sole combined screening test of the first trimester, or integrated screening test on the increase in prenatal detection rate of Down syndrome. The diagnostics is also now performed earlier during the pregnancy and the number of invasive diagnostics procedures decreased.

• MeSH
• Biomarkers MeSH
• Chromosome Aberrations * statistics & numerical data   MeSH
• Epidemiologic Studies MeSH
• Humans MeSH
• Prenatal Diagnosis * methods   MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10-5 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17-28, 2019. © 2018 Wiley Periodicals, Inc.

• MeSH
• Autistic Disorder genetics   MeSH
• Genome-Wide Association Study * MeSH
• Chromosome Aberrations statistics & numerical data   MeSH
• Cytogenetic Analysis MeSH
• Adult MeSH
• Down Syndrome genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasms etiology   genetics   MeSH
• DNA Repair genetics   MeSH
• DNA Damage genetics   MeSH
• Promoter Regions, Genetic genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Slovakia MeSH

Chromozomové aberace jsou častou příčinou časných reprodukčních ztrát. Možnou přítomnost chromozomové aberace je možné ověřit cytogenetickým vyšetřením tkáně potraceného plodu. V rámci naší studie na Ústavu biologie a lékařské genetiky 1. lékařské fakulty Univerzity Karlovy a Všeobecné fakultní nemocnice v Praze jsme analyzovali vzorek tkáně u 233 případů časných spontánních či zamlklých potratů. Ve 212 případech byla kultivace úspěšná a celkem v 52 případech (24,5 %) byla zachycena chromozomová aberace – nejčastěji trizomie chromozomu 21, monozomie chromozomu X, triploidie a trizomie chromozomů 16 a 22. Celková četnost chromozomových aberací byla v našem souboru spíše nižší oproti obdobným studiím. I s ohledem na další ukazatele předpokládáme, že by příčinou mohla být kontaminace některých vzorků mateřskými buňkami, což ale nelze u rutinního cytogenetického vyšetření předem vyloučit. Dále jsme v rámci studie potvrdili vyšší četnost chromozomových aberací v případech s vyšším věkem matky a dále pak častější zastoupení chromozomových aberací v případech potratu ve vyšších týdnech těhotenství. Tyto nálezy byly statisticky významné.

Chromosomal aberrations are common cause of early miscarriage. Possible presence of chromosomal aberration may be assessed by cytogenetic examination of the aborted fetus tissue. In our study from the Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles University and General University Hospital in Prague we analysed tissue sample from 233 early spontaneous or missed abortions. In 212 cases the cultivation process was successful. Among those – we identified 52 cases with chromosomal aberration (24,5 %). Most common aberrations were – trisomy 21, monosomy X, triploidy and trisomies of chromosomes 16 and 22. Our overall incidence of aberrations was lower – compared to similar studies. According to other indicators we suppose that this may be caused by the higher incidence of maternal cells contamination – but this phenomenon cannot be completely excluded while using classical karyotyping. We also confirmed higher incidence of chromosomal aberrations in the miscarriage cases in elder mothers and furthermore we found higher incidence of aberrations in cases from higher gestation weeks. Both trends were statistically significant.

• Keywords
• reprodukční ztráty,
• MeSH
• Chromosome Aberrations * embryology   classification   statistics & numerical data   MeSH
• Cytogenetic Analysis statistics & numerical data   MeSH
• Genetic Fitness MeSH
• Karyotyping statistics & numerical data   MeSH
• Humans MeSH
• Aborted Fetus abnormalities   cytology   MeSH
• Retrospective Studies MeSH
• Reproduction genetics   MeSH
• Abortion, Spontaneous epidemiology   etiology   MeSH
• Pregnancy MeSH
• Age Factors MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: In the adult population with newly diagnosed chronic myeloid leukemia (CML), variant translocations are usually not considered to be impairing the prognosis, whereas some additional cytogenetic abnormalities (ACAs) are associated with a negative impact on survival. Because of the rarity of CML in the pediatric population, such abnormalities have not been investigated in a large group of children with CML. METHODS: The prognostic relevance of variant t(9;22) and ACAs at diagnosis was assessed in 301 children with CML in the chronic phase who were enrolled in the International Registry for Chronic Myeloid Leukemia in Children and Adolescents. RESULTS: Overall, 19 children (6.3%) presented with additional cytogenetic findings at diagnosis: 5 children (1.7%) had a variant t(9;22) translocation, 13 children (4.3%) had ACAs, and 1 had both. At 3 years, for children with a classic translocation, children with ACAs, and children with a variant t(9;22) translocation who were treated with imatinib as frontline therapy, the probability of progression-free survival (PFS) was 95% (95% confidence interval [CI], 91%-97%), 100%, and 75% (95% CI, 13%-96%), respectively, and the probability of overall survival (OS) was 98% (95% CI, 95%-100%), 100% (95% CI, 43%-98%), and 75% (95% CI, 13%-96%), respectively. No statistical difference was observed between the patients with classic cytogenetic findings and those with additional chromosomal abnormalities in terms of PFS and OS. CONCLUSIONS: In contrast to adults with CML, additional chromosomal abnormalities observed at diagnosis do not seem to have a significant prognostic impact. Cancer 2017;123:3609-16. © 2017 American Cancer Society.

• MeSH
• Survival Analysis MeSH
• Chromosome Aberrations statistics & numerical data   MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis   drug therapy   genetics   mortality   MeSH
• Genetic Predisposition to Disease epidemiology   MeSH
• Internationality MeSH
• Kaplan-Meier Estimate MeSH
• Real-Time Polymerase Chain Reaction methods   MeSH
• Humans MeSH
• Chromosomes, Human, Pair 22 genetics   MeSH
• Chromosomes, Human, Pair 9 genetics   MeSH
• Follow-Up Studies MeSH
• Statistics, Nonparametric MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Drug Administration Schedule MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Klasická cytogenetická analýza buněk kostní dřeně je základním standardem pro vyšetření pacientů s myelodysplastickými syndromy (MDS). Pro detekci chromozomových aberací v jádrech nedělících se buněk lze využít interfázní fluorescenční in situ hybridizaci (I-FISH). Jako alternativu k I-FISH analýze buněk kostní dřeně jsme v této práci využili metodu I-FISH pro analýzu chromozomových aberací v CD34+ buňkách cirkulujících v periferní krvi. Cílem bylo hodnotit metodou I-FISH frekvenci chromozomových aberací v CD34+ buňkách izolovaných z periferní krve, porovnat ji s výsledky I-FISH analýz buněk kostní dřeně a posoudit možnost využití této metody k monitorování úspěšnosti terapie u nemocných s MDS. Vyšetřili jsme celkem 22 vzorků CD34+ buněk separovaných z periferní krve šestnácti pacientů s MDS (13 žen; 3 muži; 11krát 5q- syndrom, 4krát MDS RCMD a 1krát MDS/MPS). Čtyři nemocní byli vyšetřeni opakovaně. Metoda I-FISH na separovaných CD34+ buňkách potvrdila předchozí nálezy v buňkách kostní dřeně u všech vyšetřených pacientů – 14 nemocných mělo deleci chromozomu 5 v oblasti 5q31, u jednoho nemocného byla nalezena delece chromozomu 20 v oblasti 20q11q12 a u jednoho nemocného monozomie chromozomu 7. V naší práci jsme prokázali, že izolace CD34+ buněk a následná I-FISH analýza je praktická neinvazivní metoda, která dokáže zachytit specifické chromozomové abnormality přítomné v kostní dřeni. Vyšetření lze tedy vhodně využít pro šetrnější kontrolu onemocnění a ke sledování dynamiky patologického klonu po léčbě.

Classical cytogenetic analysis of bone marrow cells is the standard for evaluating chromosomal aberrations in patients with myelodysplastic syndromes (MDS). However, there are several factors affecting the success of this method, such as the degree of cell proliferation, quality of preparations or size of pathological clone. In these cases, it is possible to use interphase fluorescence in situ hybridization (I-FISH), which allows detection of chromosomal aberrations in the nuclei of interphase cells. In this study, we used the I-FISH method to screen chromosomal aberrations in peripheral blood circulating CD34+ cells. Our objective was to evaluate the frequency of chromosomal aberrations in CD34+ cells isolated from peripheral blood, to compare this with the results of I-FISH analysis of bone marrow cells and to assess the significance of this method for monitoring the effect of therapy in patients with MDS. We examined 22 samples of CD34+ cells separated from the peripheral blood of 16 patients with MDS (13 females, 3 males; 11 x 5q- syndromes, 4x MDS RCMD and 1x MDS/MPS). Four patients were investigated repeatedly. I-FISH on the separated CD34+ cells confirmed the prior findings in bone marrow in all the patients examined – 14 patients had deletion of chromosome 5 in the 5q31 region, one patient had deletion of chromosome 20q11q12 and one patient had monosomy of chromosome 7. In our work, we demonstrated that isolation of CD34+ cells followed by I-FISH analysis is a practical, non-invasive method that can detect specific chromosomal abnormalities present in the pathological clone. This method has a predictive value and can be used for continuous disease control as well as for monitoring the pathological clone dynamics following treatment.

• MeSH
• Antigens, CD34 * blood   MeSH
• Bone Marrow Cells pathology   MeSH
• Chromosome Aberrations statistics & numerical data   MeSH
• Chromosome Deletion MeSH
• Cytogenetic Analysis MeSH
• Adult MeSH
• In Situ Hybridization, Fluorescence * methods   MeSH
• Karyotyping MeSH
• Middle Aged MeSH
• Humans MeSH
• Chromosomes, Human, Pair 5 genetics   MeSH
• Young Adult MeSH
• Myelodysplastic Syndromes * diagnosis   genetics   blood   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

We aimed to investigate in detail the structural mutations after influence of actellic insecticide at different doses and different temperature conditions. We tested effects of single introduction of different doses of actellic: 48, 96, 192, and 384 mg/kg. Cytogenetic effect of actellic in bone marrow cells at different temperature regimens was studied. Following actellic administration, animals were being in two temperature regimes: normal (18-20°C) and high (37-38°C). After treatment with actellic, animals were kept within 1, 2, 4 and 8 hours at high temperature (37-38°C), i.e. in a thermostat (TV-80) with access of air. In experiments, the animals were divided into seven groups. The animals of the 1st group were administered actellic at a dose 384 mg/kg and kept under normal temperature until slaughtering. The animals of the 2nd group after administration of actellic were immediately placed in an environment with a temperature of 37-38°C. Animals of the 3rd, 4th, 5th, and 6th groups after treatment with actellic were transferred to conditions with high temperature, respectively, for 1, 2, 4 and 8 hours. The 7th group of mice was under normal temperature conditions without treatment with actellic. Our results have shown that in normal temperature conditions single exposure of actellic (384 mg/kg) did not affect the genetic apparatus of somatic cell, evidenced by the frequency of chromosome aberrations in bone marrow cells that were within the control levels. However, at high temperatures (37-38°C) the pesticide caused 6-fold larger number of chromosome aberrations in bone marrow cells, in comparison with normal conditions.

• Keywords
• Actellic,
• MeSH
• Bone Marrow Cells pathology   drug effects   ultrastructure   MeSH
• Chromosome Aberrations * chemically induced   statistics & numerical data   MeSH
• Cytogenetic Analysis statistics & numerical data   MeSH
• Insecticides * blood   adverse effects   MeSH
• Mice MeSH
• Organophosphorus Compounds blood   adverse effects   MeSH
• Statistics as Topic MeSH
• Hot Temperature MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH

Cílem naší práce bylo přispět k hodnocení zdravotního rizika kombinované inhalační a dermální expozice PAU u osob pracujících v oboru silniční stavitelství. V rámci hodnocení expoziční cesty bylo v pracovním ovzduší a na kůži exponovaných osob stanoveno 15 vybraných PAU. Zhodnocení genotoxické expozice (chromozomové aberace periferních lymfocytů) bylo provedeno před/po sezoně (jaro/podzim) vždy jednorázovým odběrem krve. Skupina pracovníků v oboru silniční stavitelství byla inhalačně exponována PAU na hladinách výrazně nižších, než jsou pracovní limity v České republice. Rovněž dle hodnocení World Health Organization (WHO) lze námi zjištěnou inhalační expozici benzo(a) pyrenu považovat za přijatelnou. Dermální expozice byla na nízké úrovni. Nalezli jsme významný nárůst chromozomových aberací periferních lymfocytů po sezoně. Tento nález však byl stále v mezích normálních hodnot. Genotoxické riziko lze považovat za nízké.

The aim of our study was to contribute to the evaluation of health risk assessments of combined inhalation and dermal exposure to PAHs amongst road construction crews. Within the framework of evaluating inhalation and dermal exposure of persons there have been determined 15 selected PAHs. Assessments of genotoxic exposure (chromosomal aberrations of peripheral lymphocytes) were performed in the spring and autumn seasons with single blood samples in each case. Road construction crews were exposed to inhaled PAHs at levels significantly lower than those stipulated by work limits in the Czech Republic. According to the World Health Organization (WHO) assessment, the detected inhalation exposure to benzo(a) pyrene is also acceptable. Dermal exposure was low. We detected a significant increase in chromosomal aberrations of peripheral lymphocytes post season. This finding, however, did not exceed limit values. Genotoxic risk can be considered to be low.

• Keywords
• genotoxická rizika,
• MeSH
• Chromosome Aberrations statistics & numerical data   MeSH
• Adult MeSH
• Financing, Organized MeSH
• Risk Assessment statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• Polycyclic Aromatic Hydrocarbons analysis   adverse effects   MeSH
• Occupational Exposure analysis   MeSH
• Construction Industry MeSH
• Mutagenicity Tests MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Evaluation Study MeSH

Cílem práce byl popis a analýza údajů evidovaných v registru profesionálních expozic genotoxickým faktorům v rámci Moravskoslezského kraje (MSK). Bylo vybráno 748 osob, jež byly v registru minimálně od roku 2005 a byly v evidenci alespoň tři roky, převážně v expozici genotoxickým faktorům chemického charakteru. Průměrná délka expozice byla 15,1 let. Ze 748 osob byla cytogenetická analýza lidských periferních lymfocytů provedena u 492 osob. Ve skupině zvýšené a vysoké expozice genotoxickým látkám bylo 341 osob. Tyto výsledky ukazují na zvýšenou expozici genotoxickým látkám a mohou tím zvyšovat pravděpodobnost rizika vzniku nádorových onemocnění. Osoby, které měly opakovaně zvýšené hodnoty procenta aberantních buněk, byly následně vyřazeny z expozice, a mnohdy i z evidence. Z evidence byly vyřazeny také osoby, které zemřely, nebo byl pracovní poměr ukončen. Tím dochází k přerušení pravidelných kontrol v době, kdy je největší předpoklad projevu biologického účinku dlouhodobé expozice genotoxickým látkám z důvodu latence a dochází tím i k přerušení poskytování cílené preventivní péče.

The objective of the work was to describe and analyze data kept in the files of the registry of occupational exposure to genotoxic factors within the Moravia-Silesia region. We selected 748 persons whose data were kept in the registry since 2005 for at least three years, mostly in the exposure to genotoxic factors of chemical nature. The mean duration of exposure was 15.1 years. Cytogenetic analysis of human peripheral lymphocytes was performed 492 subjects out of the 748 individuals. The group of increased and high exposure to genotoxic factors included 341 persons. The results indicate an increase exposure to genotoxic factors and thereby increased probability in development of tumor diseases. The persons whose values of percentage of aberrant cells had been repeatedly elevated were subsequently laid off the exposure and often also excluded from the register. Moreover, persons who died or were laid off the job were also excluded from the register. In this way, regular follow up was disrupted at the time, when there is the highest possibility that the biological effect of long-term exposure to genotoxic substances becomes manifest due to latency period the provision of preventive care was also disrupted.

• Keywords
• genotoxické riziko, cytogenetická analýza lidských periferních lymfocytů, registr, REGEX,
• MeSH
• Chromosome Aberrations chemically induced   statistics & numerical data   MeSH
• Risk Assessment methods   MeSH
• Carcinogens * classification   toxicity   MeSH
• Humans MeSH
• Lymphocytes cytology   MeSH
• Mutagens adverse effects   toxicity   MeSH
• Neoplasms genetics   chemically induced   prevention & control   MeSH
• Occupational Diseases chemically induced   prevention & control   MeSH
• Occupational Exposure * adverse effects   MeSH
• Primary Prevention methods   organization & administration   MeSH
• Registries * statistics & numerical data   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Geographicals
• Czech Republic MeSH

AIMS: The aim of our study was to scan for cryptic rearrangements using the multiplex ligation probe amplification method in a cohort of 64 probands with mental retardation or developmental delays in combination with at least one of the following symptoms: hypotonia after birth, congenital anomalies, or face dysmorphisms; but without a positive cytogenetic finding. The study contributes to the knowledge of microdeletion syndromes and helps disclose their natural phenotypic variability. RESULTS: In total, 10 positives (16%) were detected, particularly 3 duplications (Xpter-p22.32; 17p11.2; 22q11) and 6 different deletions (1p36; 7q11.23; 10p15; 15q11-q13; 17p11.2; 17p13.3), 1 of these in 2 probands. Besides the well-characterized syndromes, less-often described rearrangements with ambiguous phenotype associations were also detected. CONCLUSIONS: Some rearrangements, particularly duplications, are associated with vague phenotypes; and their frequency could be underestimated.

• MeSH
• Chromosome Aberrations statistics & numerical data   MeSH
• Chromosome Deletion MeSH
• Chromosome Disorders epidemiology   genetics   MeSH
• Child MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Chromosomes, Human, Pair 1 genetics   MeSH
• Chromosomes, Human, Pair 7 MeSH
• Intellectual Disability epidemiology   genetics   MeSH
• Adolescent MeSH
• Genetics, Population MeSH
• Prader-Willi Syndrome epidemiology   genetics   MeSH
• Child, Preschool MeSH
• Williams Syndrome epidemiology   genetics   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH