Molecular and cellular pediatrics最新文献

{"title":"Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency.","authors":"Stefanie Zorn, Julia von Schnurbein, Katja Kohlsdorf, Christian Denzer, Martin Wabitsch","doi":"10.1186/s40348-020-00107-3","DOIUrl":"10.1186/s40348-020-00107-3","url":null,"abstract":"<p><strong>Background: </strong>Rare genetic variations in the leptin-melanocortin signalling pathway can severely impair appetite regulation and cause extreme obesity in early childhood.</p><p><strong>Case presentation: </strong>Our case reports describe the diagnostic and therapeutic procedures in a girl as well as in a non-related boy of non-consanguineous, German parents with severe early-onset obesity, pronounced hyperphagia, and permanent food-seeking behaviour. Excessive weight gain within the first year of life initiated extensive diagnostics without finding a causal diagnosis. Furthermore, a wide range of intensive, interdisciplinary, and behavioural therapies for weight control were unsuccessful. Prior to bariatric surgery, the 18-year-old girl and the 14-year-old boy reached a BMI of 67.7 kg/m² and 55.2 kg/m², respectively. However, even surgical outcomes were unsatisfactory. A subsequently initiated genetic analysis including sequencing of the leptin receptor gene revealed compound heterozygous variants as a cause of the severe early-onset obesity in both patients (c.2598-3_2607delTAGAATGAAAAAG and c.2227 T>C; c.1874G>A and c.2051A>C). Both patients were enrolled in the clinical study RM-493-015 and treated with melanocortin receptor agonist setmelanotide. Currently, they are still on setmelanotide treatment in the extension trial RM-493-022.</p><p><strong>Conclusion: </strong>Our case report illustrates the urgent necessity of early genetic diagnostics in children with severe early-onset obesity to avoid frustrating and potentially damaging therapies. Thus, genetic examination should precede bariatric surgery. In the future, several pharmacological therapies will be available for some forms of monogenetic obesity.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"7 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2020-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38559631","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":"Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts' consensus.","authors":"Gerhard Binder,&nbsp;Dirk Schnabel,&nbsp;Thomas Reinehr,&nbsp;Roland Pfäffle,&nbsp;Helmuth-Günther Dörr,&nbsp;Markus Bettendorf,&nbsp;Berthold Hauffa,&nbsp;Joachim Woelfle","doi":"10.1186/s40348-020-00108-2","DOIUrl":"https://doi.org/10.1186/s40348-020-00108-2","url":null,"abstract":"<p><p>Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained.There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"7 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2020-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00108-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38663549","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":"A case of recurrent herpes simplex 2 encephalitis, VZV reactivations, and dominant partial interferon-gamma-receptor-1 deficiency supports relevance of IFNgamma for antiviral defense in humans.","authors":"Julia Körholz,&nbsp;Nicole Richter,&nbsp;Jochen Schäfer,&nbsp;Catharina Schuetz,&nbsp;Joachim Roesler","doi":"10.1186/s40348-020-00106-4","DOIUrl":"https://doi.org/10.1186/s40348-020-00106-4","url":null,"abstract":"<p><strong>Background: </strong>Unlike infections with mycobacteria, reports of unusual viral infections in interferon-gamma-receptor (IFNγR) deficient patients are scarce. Therefore, discussion about increased susceptibility to viral infections in these patients is ongoing.</p><p><strong>Case presentation: </strong>We describe a 51-year-old male with dominant partial interferon-gamma-receptor-1 (IFNγR1)-deficiency and recurrent Herpes simplex 2 meningoencephalitis as well as other viral reactivations since childhood.</p><p><strong>Conclusions: </strong>This case further confirms an enhanced risk for viral disease in IFNγR-deficient patients and a role of interferon gamma for human antiviral defense.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"7 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2020-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00106-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38485079","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":"A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney.","authors":"Ines Marek,&nbsp;Karl Friedrich Hilgers,&nbsp;Wolfgang Rascher,&nbsp;Joachim Woelfle,&nbsp;Andrea Hartner","doi":"10.1186/s40348-020-00105-5","DOIUrl":"https://doi.org/10.1186/s40348-020-00105-5","url":null,"abstract":"<p><p>Glomerulonephritis results in a dysregulation of glomerular cells and may end up in chronic alterations and subsequent loss of renal function. Therefore, understanding mechanisms, which contribute to maintain glomerular integrity, is a pivotal prerequisite for therapeutic interventions. The alpha-8 integrin chain seems to be an important player to maintain glomerular homeostasis by conferring mechanical stability and functional support for the renal capillary tuft.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"7 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00105-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38440651","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":"Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report.","authors":"Nami Mohammadian Khonsari,&nbsp;Sahar Mohammad Poor Nami,&nbsp;Benyamin Hakak-Zargar,&nbsp;Tessa Voth","doi":"10.1186/s40348-020-00104-6","DOIUrl":"https://doi.org/10.1186/s40348-020-00104-6","url":null,"abstract":"<p><strong>Background: </strong>Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead to Laron syndrome (LS), one of the several disorders that are collectively called growth hormone insensitivity syndrome (GHI). Another example is Floating-Harbor syndrome (FHS), a rare autosomal dominant due to mutations in the SRCAP gene that can also result in short stature.</p><p><strong>Case presentation: </strong>We report the case of a 6-year-old female with concomitant mutations in the three genes mentioned above. The mutations reported here were found on genetic studies and are usually benign, causing a variant of undetermined significance. However, our patient's phenotype could only be explained by the compounded effects of pathogenic mutations of these genes. Some of the same mutations were also found in the patient's father and her paternal grandfather. Both also presented with short stature, though not to the same degree as our patient. While these mutations are often reported to be insignificant, they gave rise to severe short stature and a specific phenotype in the patient when presented together. We think that even though the GHI spectrum is inherited through an autosomal recessive pattern, the sum of these heterozygous mutations resulted in severe short stature despite the limited GHI seen in our patient, the father, and the grandfather, through a rare ACAN and SRCAP mutation that, to our knowledge, has not been previously reported as a pathogenic mutation in the literature.</p><p><strong>Conclusion: </strong>We investigated the possible synergistic effects of these variations on exacerbation or masking of the signs and symptoms of GHI with the hope of providing a better understanding of these genes and their function through our rare case.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"7 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2020-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-00104-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38484173","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":"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":"7 1","pages":"12"},"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":"7 1","pages":"10"},"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":"7 1","pages":"9"},"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":"7 1","pages":"8"},"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":"7 1","pages":"7"},"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}