Dataset Information

Cytogenetic and Molecular Genetic Characterization of Children with Short Stature.

ABSTRACT: BACKGROUND:The deficiency of SHOX gene (short stature homeobox-containing gene) has been recognized as the most frequent monogenetic cause of short stature. SHOX gene has been associated with short stature in Turner syndrome and Leri Weill dyschondrosteosis as well with non-syndromic idiopathic short stature. The aim of this study was to determine the frequency of SHOX deletions and mutations in a cohort of Slovenian children with short stature, and to delineate indications for routine SHOX gene mutation screening. METHODS AND RESULTS:40 selected subjects with idiopathic short stature were screened for entire SHOX gene deletion and for mutations in the SHOX gene coding region (exon 2 to 6), together with sequences flanking the exon-intron boundaries. FISH analysis on metaphase and interphase spreads revealed no entire gene deletion. Additionally, no pathogenic point mutations or smaller deletion/duplications were identified in this study group. CONCLUSIONS:SHOX gene deletions and point mutations are not a common cause of idiopathic short stature in a cohort of Slovenian children with short stature. Therefore, the frequency of SHOX mutations must be much lower as expected based on the reported data.

SUBMITTER: Hovnik T

PROVIDER: S-EPMC4820174 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Cytogenetic and Molecular Genetic Characterization of Children with Short Stature.

Hovnik Tinka T Šmigoc Schweiger Darja D Kotnik Primož P Kovač Jernej J Battelino Tadej T Trebušak Podkrajšek Katarina K

Zdravstveno varstvo 20150313 2

<h4>Background</h4>The deficiency of SHOX gene (short stature homeobox-containing gene) has been recognized as the most frequent monogenetic cause of short stature. SHOX gene has been associated with short stature in Turner syndrome and Leri Weill dyschondrosteosis as well with non-syndromic idiopathic short stature. The aim of this study was to determine the frequency of SHOX deletions and mutations in a cohort of Slovenian children with short stature, and to delineate indications for routine S ...[more]

PMID: 27646915

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Project description:BackgroundAs a result of the essential role of oestrogens in epiphyseal closure, aromatase inhibitors have been trialled as an intervention to improve height outcomes in male children and adolescents by inhibiting the conversion of testosterone to oestradiol.ObjectivesTo assess the effects of aromatase inhibitors in male children and adolescents with short stature.Search methodsTo identify relevant trials, we searched the Cochrane Library (2014, Issue 7), MEDLINE, EMBASE, and the World Health Organization (WHO) ICTRP trial register from their inception until August 2014. In addition, we conducted citation searches and screened reference lists of included trials.Selection criteriaWe included randomised controlled trials (RCTs) if they compared use of an aromatase inhibitor with placebo in male children and adolescents with short stature.Data collection and analysisTwo authors independently screened titles and abstracts for relevance. Both authors carried out screening for inclusion, data extraction, and risk of bias assessment, with any disagreements resolved following discussion. We assessed trials for quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. We contacted study authors regarding missing information. Primary outcomes were final or near-final height, adverse events, and health-related quality of life. Secondary outcomes included all-cause mortality, cognitive outcomes, socioeconomic effects, laboratory measures, short-term growth parameters, and assessment of effects on bone health. Meta-analysis was not appropriate due to the substantial clinical heterogeneity between trials; we presented the findings of the review in narrative format.Main resultsWe included four RCTs involving 207 participants (84 on interventions) in the review. Trials included males with constitutional delay of growth and puberty (CDGP), idiopathic short stature (ISS), and growth hormone (GH) deficiency. Three of the trials had an overall low or unclear risk of bias for primary outcomes. Short-term growth outcomes, such as predicted adult height, improved in all trials. Just one trial reported the primary outcome of final and near-final height as an extension under non-randomised conditions. None of the trials assessed health-related quality of life. One publication provided detailed information regarding the incidence of adverse events. A significant proportion (45%) of prepubertal boys with ISS treated with letrozole developed mild morphological abnormalities of their vertebrae, compared with none in the placebo group.Authors' conclusionsAvailable evidence suggested that aromatase inhibitors improved short-term growth outcomes. There was no evidence to support an increase in final adult height, based on limited data, with only one of four trials publishing final height data under non-randomised conditions.

Project description:ObjectiveIdiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS.MethodsFrozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experiments in vitro were used to further explore the effects of crucial proteins on endochondral ossification.ResultsA total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p <0.001). Finally, the western blotting analysis confirmed the expression levels of OCN, OPN, RUNX2, and Collagen X were downregulated in chondrocytes, and the outcome of Collagen II was upregulated.ConclusionOur study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.

Dataset Information

Cytogenetic and Molecular Genetic Characterization of Children with Short Stature.

Publications

Cytogenetic and Molecular Genetic Characterization of Children with Short Stature.

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