Molecular and cellular pediatrics最新文献

{"title":"Early clinical course after hematopoietic stem cell transplantation in children with juvenile metachromatic leukodystrophy.","authors":"Judith Beschle,&nbsp;Michaela Döring,&nbsp;Christiane Kehrer,&nbsp;Christa Raabe,&nbsp;Ute Bayha,&nbsp;Manuel Strölin,&nbsp;Judith Böhringer,&nbsp;Andrea Bevot,&nbsp;Nadja Kaiser,&nbsp;Benjamin Bender,&nbsp;Alexander Grimm,&nbsp;Peter Lang,&nbsp;Ingo Müller,&nbsp;Ingeborg Krägeloh-Mann,&nbsp;Samuel Groeschel","doi":"10.1186/s40348-020-00103-7","DOIUrl":"https://doi.org/10.1186/s40348-020-00103-7","url":null,"abstract":"<p><strong>Background: </strong>Long-term outcomes of hematopoietic stem cell transplantation (HSCT) in children with juvenile metachromatic leukodystrophy (MLD) have been investigated systematically, while short-term effects of HSCT on the course of the disease remain to be elucidated.</p><p><strong>Results: </strong>In this study, the clinical course was evaluated over the first 24 months following HSCT, conducted at our center in 12 children with juvenile MLD (mean follow-up 6.75 years, range 3-13.5) and compared with 35 non-transplanted children with juvenile MLD. Motor function (GMFM-88 and GMFC-MLD), cognitive function (FSIQ), peripheral neuropathy (tibial nerve conduction velocity), and cerebral changes (MLD-MR severity score) were tested prospectively. Seven children remained neurologically stable over a long period, five exhibited rapid disease progression over the first 12 to 18 months after transplantation. In the latter, time from first gross motor symptoms to loss of independent walking was significantly shorter compared with non-transplanted patients at the same stage of disease (p < 0.02). Positive prognostic factors were good motor function (GMFM = 100%, GMFC-MLD = 0) and a low MR severity score (≤ 17) at the time of HSCT.</p><p><strong>Conclusions: </strong>Our results show that if disease progression occurs, this happens early on after HSCT and proceeds faster than in non-transplanted children with juvenile MLD, indicating that HSCT may trigger disease progression.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00103-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38365210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nup133 and ERα mediate the differential effects of hyperoxia-induced damage in male and female OPCs.","authors":"Donna Elizabeth Sunny,&nbsp;Elke Hammer,&nbsp;Sebastian Strempel,&nbsp;Christy Joseph,&nbsp;Himanshu Manchanda,&nbsp;Till Ittermann,&nbsp;Stephanie Hübner,&nbsp;Frank Ulrich Weiss,&nbsp;Uwe Völker,&nbsp;Matthias Heckmann","doi":"10.1186/s40348-020-00102-8","DOIUrl":"https://doi.org/10.1186/s40348-020-00102-8","url":null,"abstract":"<p><strong>Background: </strong>Hyperoxia is a well-known cause of cerebral white matter injury in preterm infants with male sex being an independent and critical risk factor for poor neurodevelopmental outcome. Sex is therefore being widely considered as one of the major decisive factors for prognosis and treatment of these infants. But unfortunately, we still lack a clear view of the molecular mechanisms that lead to such a profound difference. Hence, using mouse-derived primary oligodendrocyte progenitor cells (OPCs), we investigated the molecular factors and underlying mechanisms behind the differential response of male and female cells towards oxidative stress.</p><p><strong>Results: </strong>We demonstrate that oxidative stress severely affects cellular functions related to energy metabolism, stress response, and maturation in the male-derived OPCs, whereas the female cells remain largely unaffected. CNPase protein level was found to decline following hyperoxia in male but not in female cells. This impairment of maturation was accompanied by the downregulation of nucleoporin and nuclear lamina proteins in the male cells. We identify Nup133 as a novel target protein affected by hyperoxia, whose inverse regulation may mediate this differential response in the male and female cells. Nup133 protein level declined following hyperoxia in male but not in female cells. We show that nuclear respiratory factor 1 (Nrf1) is a direct downstream target of Nup133 and that Nrf1 mRNA declines following hyperoxia in male but not in female cells. The female cells may be rendered resistant due to synergistic protection via the estrogen receptor alpha (ERα) which was upregulated following hyperoxia in female but not in male cells. Both Nup133 and ERα regulate mitochondrial function and oxidative stress response by transcriptional regulation of Nrf1.</p><p><strong>Conclusions: </strong>These findings from a basic cell culture model establish prominent sex-based differences and suggest a novel mechanism involved in the differential response of OPCs towards oxidative stress. It conveys a strong message supporting the need to study how complex cellular processes are regulated differently in male and female brains during development and for a better understanding of how the brain copes up with different forms of stress after preterm birth.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00102-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38308494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteogenesis imperfecta-pathophysiology and therapeutic options.","authors":"Julia Etich,&nbsp;Lennart Leßmeier,&nbsp;Mirko Rehberg,&nbsp;Helge Sill,&nbsp;Frank Zaucke,&nbsp;Christian Netzer,&nbsp;Oliver Semler","doi":"10.1186/s40348-020-00101-9","DOIUrl":"https://doi.org/10.1186/s40348-020-00101-9","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased bone fragility as well as additional, variable extraskeletal symptoms. Here, we present an overview of the genetic heterogeneity and pathophysiological background of OI as well as OI-related bone fragility disorders and highlight current therapeutic options.The most common form of OI is caused by mutations in the two collagen type I genes. Stop mutations usually lead to reduced collagen amount resulting in a mild phenotype, while missense mutations mainly provoke structural alterations in the collagen protein and entail a more severe phenotype. Numerous other causal genes have been identified during the last decade that are involved in collagen biosynthesis, modification and secretion, the differentiation and function of osteoblasts, and the maintenance of bone homeostasis.Management of patients with OI involves medical treatment by bisphosphonates as the most promising therapy to inhibit bone resorption and thereby facilitate bone formation. Surgical treatment ensures pain reduction and healing without an increase of deformities. Timely remobilization and regular strengthening of the muscles by physiotherapy are crucial to improve mobility, prevent muscle wasting and avoid bone resorption caused by immobilization. Identification of the pathomechanism for SERPINF1 mutations led to the development of a tailored mechanism-based therapy using denosumab, and unraveling further pathomechanisms will likely open new avenues for innovative treatment approaches.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00101-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38274994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype correlations in children and adolescents with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.","authors":"Helmuth-Günther Dörr,&nbsp;Nadja Schulze,&nbsp;Markus Bettendorf,&nbsp;Gerhard Binder,&nbsp;Walter Bonfig,&nbsp;Christian Denzer,&nbsp;Desiree Dunstheimer,&nbsp;Kirsten Salzgeber,&nbsp;Heinrich Schmidt,&nbsp;Karl Otfried Schwab,&nbsp;Egbert Voss,&nbsp;Martin Wabitsch,&nbsp;Joachim Wölfle","doi":"10.1186/s40348-020-00100-w","DOIUrl":"https://doi.org/10.1186/s40348-020-00100-w","url":null,"abstract":"<p><strong>Background: </strong>Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by mutations in the active 21-hydroxylase gene (CYP21A2). The clinical symptoms can vary greatly. To date, no systematic studies have been undertaken in Germany.</p><p><strong>Aims: </strong>Description of the phenotype, evaluation of the diagnostics and genotype-phenotype correlation PATIENTS AND METHODOLOGY: Retrospective analysis of the data of 134 patients (age range 0.1-18.6 years) in a multicentre study covering 10 paediatric endocrinology centres in Bavaria and Baden-Württemberg. The data was gathered on site from the medical records. Two hundred and thirty-three alleles with a mutation of the CYP21A2 gene were identified in 126 patients. A genotype-phenotype correlation of the mutation findings was undertaken (C1, severe/mild; C2, mild/mild). Individuals with a heterozygous mutation of the CYP21A2 were also included (C3). The data was collected with the approval of the ethics committee of the University Hospital of Erlangen during the period of 2014 and 2015. RESULTS (MW ± SD): One hundred and seventeen out of 134 patients (115 f, 29 m) were symptomatic. The chronological age (CA) at diagnosis was 7.1 ± 4.4 years. The most frequent symptom (73.5%) was premature pubarche. The height-SDS on diagnosis was 0.8 ± 1.3 and the BMI-SDS was 0.8 ± 1.2. Bone age (BA) was ascertained in 82.9% of the symptomatic patients. The difference between BA and CA was 1.9 ± 1.4 years. Basal 17OHP concentrations were 14.5 ± 19.1 ng/ml (18 patients < 2 ng/ml). In total, 58.1% mild and 34.7% severe mutations were found. The most common mutation was p.Val281Leu (39.1%); 65.8% of the patients could be allocated to group C1. No phenotypical differences were found between the 3 mutation groups. The 17OHP levels (basal and after ACTH) in the standard ACTH stimulation test were highest in group C1 and also significantly higher in group C2 as in C3, the ACTH-stimulated cortisol levels (ng/ml) were significantly lower in groups C1 (192.1 ± 62.5) and C2 (218 ± 50) than in C3 (297.3 ± 98.7).</p><p><strong>Conclusion: </strong>Most of the patients have symptoms of mild androgenisation. Male patients are underdiagnosed. Diagnostics are not standardised. Differences between the types of mutations are found in the hormone concentrations but not in phenotype. We speculate that further, as yet not clearly defined, factors are responsible for the development of the respective phenotypes.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00100-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38145181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation biomarkers of future health outcomes in children.","authors":"Shivanthan Shanthikumar,&nbsp;Melanie R Neeland,&nbsp;Jovana Maksimovic,&nbsp;Sarath C Ranganathan,&nbsp;Richard Saffery","doi":"10.1186/s40348-020-00099-0","DOIUrl":"https://doi.org/10.1186/s40348-020-00099-0","url":null,"abstract":"<p><p>Biomarkers which predict future health outcomes are key to the goals of precision health. Such biomarkers do not have to be involved in the causal pathway of a disease, and their performance is best assessed using statistical tests of clinical performance and evaluation of net health impact. DNA methylation is the most commonly studied epigenetic process and represents a potential biomarker of future health outcomes. We review 25 studies in non-oncological paediatric conditions where DNA methylation biomarkers of future health outcomes are assessed. Whilst a number of positive findings have been described, the body of evidence is severely limited by issues with outcome measures, tissue-specific samples, accounting for sample cell type heterogeneity, lack of appropriate statistical testing, small effect sizes, limited validation, and no assessment of net health impact. Future studies should concentrate on careful study design to overcome these issues, and integration of DNA methylation data with other 'omic', clinical, and environmental data to generate the most clinically useful biomarkers of paediatric disease.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00099-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38133620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infant formula with cow's milk fat and prebiotics affects intestinal flora, but not the incidence of infections during infancy in a double-blind randomized controlled trial.","authors":"Antonia Nomayo,&nbsp;Andreas Schwiertz,&nbsp;Rainer Rossi,&nbsp;Katharina Timme,&nbsp;Janine Foster,&nbsp;Richard Zelenka,&nbsp;Josef Tvrdik,&nbsp;Frank Jochum","doi":"10.1186/s40348-020-00098-1","DOIUrl":"https://doi.org/10.1186/s40348-020-00098-1","url":null,"abstract":"<p><strong>Background: </strong>The postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy. Specific ingredients in human milk, such as prebiotic human milk oligosaccharides and a specifically structured fat composition with high proportion of beta-palmitic acid (beta-PA) promote the growth of intestinal bifidobacteria, which are associated with favorable effects on infants' health. The present study investigates whether addition of prebiotic galactooligosaccharides (GOS) in combination with higher amounts of beta-PA from cow's milk fat in infant formula positively affects gut microbiota and the incidence of infections in formula-fed infants.</p><p><strong>Methods: </strong>In a double-blind controlled trial, formula-fed infants were randomly assigned to either receive an experimental formula containing a higher proportion of beta-PA (20-25%) from natural cow's milk fat, and a prebiotic supplement (0.5 g GOS/100 ml), or a standard infant formula with low beta-PA (< 10%), without prebiotics. A breast-fed reference group was also enrolled. After 12 weeks, fecal samples were collected to determine the proportion of fecal bifidobacteria. The number of infections during the first year of life was recorded.</p><p><strong>Results: </strong>After 12 weeks, the proportion of fecal bifidobacteria was significantly higher in infants receiving formula with high beta-PA and GOS compared to control, and was similar to the breast-fed group (medians 8.8%, 2.5%, and 5.0% respectively; p < 0.001). The incidence of gastrointestinal or other infections during the first year of life did not differ between groups.</p><p><strong>Conclusions: </strong>The combination of higher amounts of beta-PA plus GOS increased significantly the proportion of fecal bifidobacteria in formula-fed infants, but did not affect the incidence of infections.</p><p><strong>Trial registration: </strong>The study protocol was registered with Clinical Trials (Protocol Registration and Results System Trial ID: NCT01603719 ) on 05/15/2012 (retrospectively registered).</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00098-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38109048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-inflammatory cytokine ratios determine the clinical course of febrile neutropenia in children receiving chemotherapy.","authors":"Mira Siegmund,&nbsp;Julia Pagel,&nbsp;Tasja Scholz,&nbsp;Jan Rupp,&nbsp;Christoph Härtel,&nbsp;Melchior Lauten","doi":"10.1186/s40348-020-00097-2","DOIUrl":"https://doi.org/10.1186/s40348-020-00097-2","url":null,"abstract":"<p><strong>Background: </strong>Febrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim of this study to investigate cytokine profiles as potential biomarkers using in-vitro sepsis models to differentiate between distinct clinical courses of febrile neutropenia (FN).</p><p><strong>Methods: </strong>We conducted an observational study in FN episodes of pediatric oncology patients. Courses of neutropenia were defined as severe in case of proven blood stream infection or clinical evidence of complicated infection. We collected blood samples at various time points from the onset of FN and stimulated ex vivo with lipopolysaccharide (LPS) and Staphylococcus epidermidis (SE) for 24 h. Twenty-seven cytokine levels were measured in the whole blood culture supernatants by a multiplex immunoassay system.</p><p><strong>Results: </strong>Forty-seven FN episodes from 33 children were investigated. IL-8, IL-1β, and MCP-1 expression increased significantly over time. IL-8, MIP-1α, MIP-1β, MCP-1, and TNF-α showed significantly lower concentration in patients with a clinically severe course of the FN.</p><p><strong>Conclusions: </strong>Distinct patterns of cytokine profiles seem to be able to determine infectious FN and to predict the severity of its clinical course. If these data can be verified in a multi-centre setting, this may finally lead to an individualized treatment strategy facilitating antibiotic stewardship in these patients.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38030034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring.","authors":"M R Alcorta-García,&nbsp;C N López-Villaseñor,&nbsp;G Sánchez-Ferrer,&nbsp;H Flores-Mendoza,&nbsp;F Castorena-Torres,&nbsp;M A Aguilar-Torres,&nbsp;C M Sepúlveda-Treviño,&nbsp;J A Hernández-Hernández,&nbsp;R C López-Sánchez,&nbsp;V J Lara-Díaz","doi":"10.1186/s40348-020-00096-3","DOIUrl":"https://doi.org/10.1186/s40348-020-00096-3","url":null,"abstract":"<p><strong>Background: </strong>To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism.</p><p><strong>Results: </strong>In 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R² = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks.</p><p><strong>Conclusion: </strong>Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00096-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37990935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shedding light on pediatric diseases: multispectral optoacoustic tomography at the doorway to clinical applications.","authors":"Adrian P Regensburger,&nbsp;Alexandra L Wagner,&nbsp;Jing Claussen,&nbsp;Maximilian J Waldner,&nbsp;Ferdinand Knieling","doi":"10.1186/s40348-020-00095-4","DOIUrl":"https://doi.org/10.1186/s40348-020-00095-4","url":null,"abstract":"<p><p>Optoacoustic imaging (OAI), or photoacoustic imaging (PAI), has fundamentally influenced basic science by providing high-resolution visualization of biological mechanisms. With the introduction of multispectral optoacoustic tomography (MSOT), these technologies have now moved closer to clinical applications. MSOT utilizes short-pulsed near-infrared laser light to induce thermoelastic expansion in targeted tissues. This results in acoustic pressure waves, which are used to resolve specific endo- and exogenous chromophores. Especially in the pediatric population, this non-invasive imaging approach might hold fundamental advantages compared to conventional cross-sectional imaging modalities. As this technology allows the visualization of quantitative molecular tissue composition at high spatial resolution non-invasively in sufficient penetration depth, it paves the way to personalized medicine in pediatric diseases.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00095-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37704261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Random X chromosome inactivation in patients with Klinefelter syndrome.","authors":"Kenichi Kinjo,&nbsp;Tomoko Yoshida,&nbsp;Yoshitomo Kobori,&nbsp;Hiroshi Okada,&nbsp;Erina Suzuki,&nbsp;Tsutomu Ogata,&nbsp;Mami Miyado,&nbsp;Maki Fukami","doi":"10.1186/s40348-020-0093-x","DOIUrl":"https://doi.org/10.1186/s40348-020-0093-x","url":null,"abstract":"<p><strong>Background: </strong>X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10-12 embryonic progenitor cells. To date, it remains unclear whether XCI ratios are normally preserved in Klinefelter syndrome (KS) patients with 47,XXY karyotype.</p><p><strong>Methods: </strong>We examined XCI ratios in 18 KS patients through DNA methylation analysis for the polymorphic trinucleotide locus in the AR gene. The results of the KS patients were compared to previous data from healthy young women.</p><p><strong>Results: </strong>XCI ratios in KS patients followed a normal distribution. Skewed XCI was observed in two patients, one of whom exhibited extremely skewed XCI. The frequencies of skewed and extremely skewed XCI in the KS cohort were comparable to those in healthy women.</p><p><strong>Conclusion: </strong>This study confirmed the rarity of skewed XCI in KS patients. These results indicate that the presence of a supernumerary X chromosome during the cleavage and early blastocyst stages does not affect the developmental tempo of embryos. Our data deserve further validation.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-0093-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37573993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}