Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Congenital heart defect (CHD) represents the most prevalent birth defect, and accounts for substantial morbidity and mortality in humans. Aggregating evidence demonstrates the genetic basis for CHD. However, CHD is a heterogeneous disease, and the genetic determinants underlying CHD in most patients remain unknown. In the present study, a cohort of 186 unrelated cases with CHD and 300 unrelated control individuals were recruited. The coding exons and flanking introns of the MEF2C gene, which encodes a transcription factor crucial for proper cardiovascular development, were sequenced in all study participants. The functional effect of an identified MEF2C mutation was characterized using a dual-luciferase reporter assay system. As a result, a novel heterozygous MEF2C mutation, p.R15C, was detected in an index patient with congenital double outlet right ventricle (DORV) as well as ventricular septal defect. Analysis of the proband's pedigree showed that the mutation co-segregated with CHD with complete penetrance. The missense mutation, which changed the evolutionarily conserved amino acid, was absent in 300 control individuals. Functional deciphers revealed that the mutant MEF2C protein had a significantly decreased transcriptional activity. Furthermore, the mutation significantly reduced the synergistic activation between MEF2C and GATA4, another transcription factor linked to CHD. This study firstly associates MEF2C loss-of-function mutation with DORV in humans, which provides novel insight into the molecular pathogenesis of CHD, suggesting potential implications for genetic counseling and personalized treatment of CHD patients.
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Source |
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http://dx.doi.org/10.1007/s00246-018-1822-y | DOI Listing |
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