Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies.
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PMID:15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: a series of 52 patients. 2643

Congenital heart disease (CHD) is the most common congenital disorder among live births. When associated with extracardiac abnormalities, it is characterized as a syndromic heart disease (syndromic CHD) and corresponds to 25% of all liveborn infants with a heart defect. The etiology in about 65% of the cases still remains unknown, and in about 35% of the patients, it is associated with genetic factors. In the present study, MLPA and SNP-array techniques were used to investigate a group of 47 patients with syndromic CHD. In total, 16 defects (34%) were identified, of which 12 (25.5%) were classified as pathogenic or probably pathogenic. The most frequent abnormalities were 22q11.2 deletion (22q11.2 deletion syndrome) and 7q11.23 deletion (Williams-Beuren syndrome). We also show that rarer malformations may be associated with syndromic CHD, such as 14q32.33 deletion as well as 17q25.3, 15q11.2 (BP1-BP2), 22q13.31, and 12p13.31 (SLC2A3) duplications. The present study demonstrates that CNVs are important causal factors and should be studied in patients with syndromic CHD. Furthermore, the use of MLPA as a first screening test was appropriate, as this less expensive technology detected 11 of the 12 pathogenic abnormalities (91.6%).
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PMID:Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test. 2887 6

Selenium and selenoproteins are identified as potential determinants in pathological cellular hypertrophy. Cardiomyocytes hypertrophy is a compensatory form of heart disease characterized by increased size of cardiomyocytes. However, the link between cardiac hypertrophy and Se-specific microRNA (miRNA) remains to be characterized. In the current study, we established a miR-200a-5p mimic and an inhibitor cardiomyocytes model. Cardiomyocytes hypertrophy was induced in the miR-200a-5p mimic group. Hence, we detected the glucose level of cardiomyocytes to estimate the cellular glucose uptake. The effect of miR-200a-5p overexpression and the low expression on 25 selenoproteins mRNA levels was further explored using reverse transcription polymerase chain reaction. Overexpression of miR-200a-5p elevated glucose uptake and Txnrd2, 3 expression and reduced Sepp1, Seln, Selt, and Sep15 expression in cardiomyocytes. Contrary results were observed in cardiomyocytes with the knockdown of miR-200a-5p. We next assessed glucose metabolism-related genes in cardiomyocytes. The results showed that miR-200a-5p had a negative correlation with insulin-like growth factor gene-1, insulin-like growth factor binding protein (IGFBP)1, IGFBP2, IGFBP3, IGFBP4, and IGFBP5 and had a positive correlation with Akt, glucose transporter family (GLUT)2, GLUT3, and GLUT4. These results support the involvement of selenoproteins and glucose metabolism in the control of cardiomyocytes hypertrophy by Se-specific miRNA, suggesting that miR-200a-5p inhibited the expression of stress-related selenoproteins to alter glucose transport leading to glucose metabolism disorder, eventually inducing cardiomyocytes hypertrophy. Our finding highlights a pivotal role of Se-specific miRNA and selenoproteins in cardiac hypertrophy.
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PMID:miR-200a-5p augments cardiomyocyte hypertrophy induced by glucose metabolism disorder via the regulation of selenoproteins. 3014 91

To identify whether parent-of-origin effects (POE) of the 15q11.2 BP1-BP2 microdeletion are associated with differences in clinical features in individuals inheriting the deletion, we collected 71 individuals reported with phenotypic data and known inheritance from a clinical cohort, a research cohort, the DECIPHER database, and the primary literature. Chi-squared and Mann-Whitney U tests were used to test for differences in specific and grouped clinical symptoms based on parental inheritance and proband gender. Analyses controlled for sibling sets and individuals with additional variants of uncertain significance (VOUS). Among all probands, maternal deletions were associated with macrocephaly (p = 0.016) and autism spectrum disorder (ASD; p = 0.02), while paternal deletions were associated with congenital heart disease (CHD; p = 0.004). Excluding sibling sets, maternal deletions were associated with epilepsy as well as macrocephaly (p < 0.05), while paternal deletions were associated with CHD and abnormal muscular phenotypes (p < 0.05). Excluding sibling sets and probands with an additional VOUS, maternal deletions were associated with epilepsy (p = 0.019) and paternal deletions associated with muscular phenotypes (p = 0.008). Significant gender-based differences were also observed. Our results supported POEs of this deletion and included macrocephaly, epilepsy and ASD in maternal deletions with CHD and abnormal muscular phenotypes seen in paternal deletions.
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PMID:Parent-of-Origin Effects in 15q11.2 BP1-BP2 Microdeletion (Burnside-Butler) Syndrome. 3090 40

Over the past decades, substantial advances have been made in both the early diagnosis and accurate prognosis of numerous cancers because of the impressive development of novel proteomic strategies. Selenium (Se) is an essential trace element in humans and animals. Se deficiency could lead to Keshan disease in humans, mulberry heart disease in pigs and damage of tissues including cardiac injury, apoptosis in the liver, reduction in the immune responses in spleen and cerebral lesions in chickens. However, it is well know that plasma biomarkers are not specific and also show alterations in various diseases including those caused by Se deficiency. Therefore, new definition biomarkers are needed to improve disease surveillance and reduce unnecessary chicken losses due to Se deficiency. To identify new biomarkers for Se deficiency, we performed exploratory heart, liver, spleen, muscle, vein, and artery proteomic screens to further validate the biomarkers using Venn analysis, GO enrichment, heatmap analysis, and IPA analysis. Based on the bioinformatics methods mentioned above, we found that differentially expressed genes and proteins are enriched to the PI3K/AKT/mTOR signal pathway and insulin pathway. We further used western blot to detect the expression of proteins related to the two pathways. Results showed that the components of the PI3K/AKT/mTOR signal pathway were definitely decreased in heart, liver, spleen, muscle, vein and artery tissues in the Se deficient group. Expression IGF and IGFBP2 of the insulin pathway were differentially increased in the heart, liver, and spleen in Se deficient group samples and decreased in muscle and artery. In conclusion, 5 proteins, namely PI3K, AKT, mTOR, IGF, and IGFBP2, were differentially expressed, which could be potentially useful Se deficient biomarkers. In the present study, proteomic profiling was used to elucidate protein biomarkers that distinguished Se deficient samples from the controls, which might provide a new direction for the diagnosis and targeted treatment induced by Se deficiency in chickens.
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PMID:The proteomic profiling of multiple tissue damage in chickens for a selenium deficiency biomarker discovery. 3202 57