Autori prezentujú prípad I. trimestrového potratu s klinicky suponovanou skorou formou kompletnej moly hydatidózy. Histopatologická a imunohistochemická analýza vylúčila kompletnú molu, ale histomorfologický profil naznačoval parciálnu hydatidóznu molu. Genetická analýza vylúčila parciálnu molu na základe biparentálnej kompozície genómu, ďalšie genetické analýzy odhalili trizómiu chromozómu 16. Trizómia chromozómu 16 je častou príčinou potratov v I. trimestri a môže viesť k vysoko abnormálnej histomorfológii placenty napodobňujúcej parciálnu molu. Genetické analýzy sú v týchto prípadoch rozhodujúce pre správnu diferenciálnu dia gnostiku, a teda pre stanovenie adekvátnej dispenzárnej starostlivosti a prognózy pre ďalšie gravidity.

The authors present a case of 1st trimester miscarriage where an early, complete hydatidiform mole was clinically suspected. Histopathological and immunohistochemical analyses excluded a complete mole, but the histomorphological profile was in concordance with a partial hydatidiform mole. Genetic analysis excluded a partial mole based on biparental genome composition, where further genetic analyses detected trisomy of chromosome 16. Trisomy of chromosome 16 is a frequent cause of 1st trimester abortions and may lead to highly abnormal placental histomorphology mimicking a partial mole. Genetic analyses are crucial for proper differential diagnosis and for the determination of adequate follow-up and prognosis for further pregnancies.

• MeSH
• dospělí MeSH
• lidé MeSH
• lidské chromozomy, pár 16 genetika   MeSH
• mola hydatidosa * diagnóza   genetika   klasifikace   komplikace   MeSH
• molekulární mimikry genetika   MeSH
• mutační analýza DNA klasifikace   metody   MeSH
• placenta anatomie a histologie   patologie   MeSH
• samovolný potrat etiologie   genetika   MeSH
• trizomie * genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

Non-invasive prenatal tests for the detection of fetal aneuploidies are predominantly based on the analysis of cell-free DNA (cfDNA) from the plasma of pregnant women by next-generation sequencing. The development of alternative tests for routine genetic laboratories is therefore desirable. Multiplex digital droplet PCR was used to detect 16 amplicons from chromosome 21 and 16 amplicons from chromosome 18 as the reference. Two fluorescently labeled lock nucleic acid probes were used for the detection of reaction products. The required accuracy was achieved by examining 12 chips from each patient using Stilla technology. The plasma cfDNA of 26 pregnant women with euploid pregnancies and 16 plasma samples from pregnancies with trisomy 21 were analyzed to determine the cutoff value for sample classification. The test was validated in a blind study on 30 plasma samples from pregnant patients with a risk for trisomy 21 ranging from 1:4 to 1:801. The results were in complete agreement with the results of the invasive diagnostic procedure (sensitivity, specificity, PPV, and NPV of 100%). Low cost, and speed of analysis make it a potential screening method for implementation into the clinical workflow to support the combined biochemical and ultrasound results indicating a high risk for trisomy 21.

• MeSH
• aneuploidie MeSH
• Downův syndrom * diagnóza   genetika   MeSH
• lidé MeSH
• polymerázová řetězová reakce MeSH
• prenatální diagnóza metody   MeSH
• těhotenství MeSH
• trizomie MeSH
• volné cirkulující nukleové kyseliny * genetika   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Chromosomal band 17q12 is a gene-rich region flanked by segmental duplications, making the region prone to deletions and duplications via the non-allelic homologous recombination mechanism. While deletions cause a well-described disorder with a specific phenotype called renal cysts and diabetes mellitus, the phenotype caused by reciprocal duplications is less specific, primarily because of variable expressivity, and incomplete penetrance. We present an unusual family with four children carrying the 17q12 microduplication inherited from their clinically healthy mother, who was a carrier of both the duplication and, interestingly, also of an atypical deletion of the 17q12 region. The duplication was inherited from her diabetic father and the deletion from her diabetic mother who also suffered from a renal disorder. Clinical manifestations in the family were variable, but all children showed some degree of a neurodevelopmental disorder, such as epilepsy, intellectual disability, delayed speech development, or attention deficit disorder. The simultaneous occurrence of a deletion and duplication in the same chromosomal region in one family is very rare, and to our knowledge, individuals carrying both a deletion and a duplication of this region have never been described.

• MeSH
• chromozomální delece MeSH
• duplikace chromozomů genetika   MeSH
• fenotyp MeSH
• lidé MeSH
• mentální retardace * genetika   MeSH
• mnohočetné abnormality * genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Spontánní potraty v prvním trimestru představují klinicky významný problém, který může postihnout až 15 % rozpoznaných gravidit. Příčiny časných těhotenských ztrát jsou velmi heterogenní a zahrnují faktory genetické, environmetální i imunologické. Ačkoli je hlavním úkolem patologa především vyloučení molární gravidity, může i konvenční histologické vyšetření v některých případech přispět k objasnění příčiny abortu a managementu další gravidity, zvláště v případě lézí s vysokým rizikem recidivy, které mohou vést k habituálnímu potrácení.

Spontaneous abortions in the first trimester of gravidity represent a clinically significant problem that can affect up to 15% of recognized pregnancies. The causes of early pregnancy loss are very heterogeneous and include genetic, environmental and immunological factors. Although the pathologist‘s main task is to exclude molar pregnancy, in some cases conventional histological examination can also contribute to the elucidation of the cause of miscarriage and the management of subsequent pregnancies, especially in the case of lesions with a high risk of recurrence that may lead to habitual abortion.

• MeSH
• abnormální karyotyp MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• první trimestr těhotenství MeSH
• samovolný potrat * patologie   MeSH
• těhotenství MeSH
• trizomie MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

A case of double trisomy 16 and 22 in the second pregnancy loss is presented. DNA analyses (short tandem repeats genotyping) of miscarriage specimen was indicated because of ultrasound suspicion of partial hydatidiform mole. After the partial hydatidiform mole exclusion, further DNA analyses focused on the most common aneuploidies causing pregnancy loss, detected double trisomy 16 and 22 in the product of conception. The couple was referred to clinical genetic consultation and normal parental karyotypes were proved. For further explanatory purposes, archived material from the first pregnancy loss was analyzed and trisomy of chromosome 18 was detected. By comparison of allelic profiles of the mother, father, and both losses, the maternal origin of all aneuploidies was proven what can be attributed to frequent meiosis errors, probably due to advanced maternal age (44 years at the first loss and 45 years at the second loss). In conclusion, aneuploidies can mimic partial hydatidiform mole. Genetic analysis is helpful on the one hand to rule out partial hydatidiform mole and on the other hand to identify aneuploidies and in this way to determine the cause of miscarriage.

• MeSH
• DNA MeSH
• dospělí MeSH
• lidé MeSH
• mola hydatidosa * diagnóza   genetika   MeSH
• nádory dělohy * diagnóza   genetika   MeSH
• samovolný potrat * diagnóza   genetika   MeSH
• těhotenství MeSH
• trizomie diagnóza   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

OBJECTIVE: The aim of the study was to analyze the results of screening for chromosomal aberrations in a population with a high rate of first-trimester screening and low rate of cell-free DNA testing. METHODS: The data were obtained from the National Registry of Congenital Anomalies of the Czech Republic. We calculated and compared the proportion of autosomal trisomies (Down, Edwards, and Patau syndrome) and of other chromosomal aberrations identified during prenatal diagnostics. RESULTS: We identified 3009 prenatally diagnosed cases of chromosomal aberrations in the 2012-2016 period. The number of major autosomal trisomies has increased from 329 cases (30.86 per 10,000 live births) in 2012 to 423 cases (37.41) in 2016 (p = 0.014). The numbers of other aberrations decreased from 246 cases (23.07 per 10,000) in 2012 to 217 cases (19.19) in 2016 (p = 0.017). The usage of invasive diagnostic procedures decreased from 1099.54 in 2012 to 622.73 in 2016 (per 10,000 live births). CONCLUSIONS: Our population-based study confirmed a decrease in prenatal detection of nonmajor chromosomal aberrations wherein a decrease of invasive testing occurred. With the introduction of cell-free DNA testing, further decrease of invasive procedures and detection of nonmajor aberrations may be expected.

• MeSH
• chromozomální aberace MeSH
• lidé MeSH
• Patauův syndrom MeSH
• prenatální diagnóza MeSH
• těhotenství MeSH
• trizomie * MeSH
• volné cirkulující nukleové kyseliny * MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• aberace pohlavních chromozomů MeSH
• dystonie * genetika   MeSH
• lidé MeSH
• lidské chromozomy X MeSH
• poruchy pohlavního vývoje spojené s poruchami pohlavních chromozomů * MeSH
• trizomie genetika   MeSH
• vazebné proteiny DNA v oblastech připojení k matrix * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

BACKGROUND: Recent studies suggest that duplication of the 9p24.3 chromosomal locus, which includes the DOCK8 and KANK1 genes, is associated with autism spectrum disorders (ASD), intellectual disability/developmental delay (ID/DD), learning problems, language disorders, hyperactivity, and epilepsy. Correlation between this duplication and the carrier phenotype needs further discussion. METHODS: In this study, three unrelated patients with ID/DD and ASD underwent SNP aCGH and MLPA testing. Similarities in the phenotypes of patients with 9p24.3, 15q11.2, and 16p11.2 duplications were also observed. RESULTS: All patients with ID/DD and ASD carried the 9p24.3 duplication and showed intragenic duplication of DOCK8. Additionally, two patients had ADHD, one was hearing impaired and obese, and one had macrocephaly. Inheritance of the 9p24.3 duplication was confirmed in one patient and his sibling. In one patient KANK1 was duplicated along with DOCK8. Carriers of 9p24.3, 15q11.2, and 16p11.2 duplications showed several phenotypic similarities, with ID/DD more strongly associated with duplication of 9p24.3 than of 15q11.2 and 16p11.2. CONCLUSION: We concluded that 9p24.3 is a likely cause of ASD and ID/DD, especially in cases of DOCK8 intragenic duplication. DOCK8 is a likely causative gene, and KANK1 aberrations a modulator, of the clinical phenotype observed. Other modulators were not excluded.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• chromozomální poruchy genetika   patologie   MeSH
• cytoskeletální proteiny genetika   MeSH
• dítě MeSH
• duplikace chromozomů * MeSH
• fenotyp * MeSH
• lidé MeSH
• lidské chromozomy, pár 9 genetika   MeSH
• předškolní dítě MeSH
• výměnné faktory guaninnukleotidů genetika   MeSH
• vývojové poruchy u dětí genetika   patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• lidské chromozomy, pár 9 MeSH
• novorozenec MeSH
• trizomie * diagnóza   genetika   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

The single-celled parasite Giardia intestinalis (Diplomonadida) has two equally sized nuclei in one cell. The nuclei have been considered identical. We have previously shown that they contain different chromosomal sets and proceed through the cell cycle with some asynchrony. Here, we demonstrate by fluorescence in situ hybridization that several genes from chromosome 5 are lost in one of the two nuclei of the WBc6 Giardia line. The missing segment stretches over at least 50kb near the 5' chromosome end. In both WB and WBc6 Giardia cell lines, chromosome 5 is trisomic in one nucleus and monosomic in the other nucleus. The described chromosomal deletion has always been observed at the monosomic chromosome in WBc6; however, the deletion was not detected in the parent line WB. The chromosomal segment was thus initially lost after biological cloning of WB, which gave rise to clone WBc6. We show that Giardia is capable of carrying out gene expression from only one nucleus. The two nuclei display a certain level of diversity, making each of them irreplaceable. The doubled karyomastigonts of diplomonads likely have separate functions both in the mastigont/flagellar organization and in chromosomal and gene content. To our knowledge, our results offer the first methodical approach to differentiating the two, so far indistinguishable nuclei. Copyright © 2019 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

• MeSH
• buněčné jádro genetika   MeSH
• časové faktory MeSH
• chromozomální delece MeSH
• delece genu MeSH
• Giardia lamblia * genetika   ultrastruktura   MeSH
• hybridizace in situ fluorescenční normy   MeSH
• komplementární DNA MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• mitóza MeSH
• monozomie * MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese fyziologie   MeSH
• reverzní transkripce MeSH
• RNA protozoální genetika   izolace a purifikace   MeSH
• signální transdukce MeSH
• trizomie genetika   MeSH