CITED2 Mutation and methylation in children with congenital heart disease

Xu, Min; Wu, Xiaoyun; Li, Yonggang; Yang, Xiaofei; Hu, Jihua; Zheng, Min; Tian, Jie

doi:10.1186/1423-0127-21-7

Cited by 42 publications

(50 citation statements)

References 32 publications

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“…Cited2-deficient mice show cardiac malformations, adrenal agenesis and neural crest defects. Mutations in this gene were reported to cause cardiac septal defects 30 . Of interest, fusions involving CITED2 gene have been described recently in a case of high grade undifferentiated pleomorphic sarcoma, however being the 5’ partner and fused to PRDM10 on 11q24 31 .…”

Section: Discussionmentioning

confidence: 99%

A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma

Alaggio

Zhang²,

Sung³

et al. 2016

American Journal of Surgical Pathology

217

122

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Sclerosing and spindle cell rhabdomyosarcoma (SRMS) have been recently re-classified as a stand-alone pathologic entity, separate from embryonal RMS (ERMS). Genetically a subset of the congenital cases display NCOA2 gene rearrangements, while tumors occurring in older children or adults harbor MYOD1 gene mutations with or without coexisting PIK3CA mutations. Despite these recent advances, a significant number of tumors lack known genetic alterations. In this study we sought to investigate a large group of pediatric spindle cell/sclerosing RMS, spanning a diverse clinical and pathologic spectrum, by using a combined FISH, targeted DNA and whole transcriptome sequencing methodology for a more definitive molecular classification. A total of 26 spindle and sclerosing RMS cases were selected from the two participating Institutions for the molecular analysis. Ten of the 11 congenital/infantile SRMS showed recurrent fusion genes: with novel VGLL2 rearrangements seen in 7 (63%), including VGLL2-CITED2 fusion in 4 and VGLL2-NCOA2 in 2 cases. Three (27%) cases harbored the previously described NCOA2 gene fusions, including TEAD1-NCOA2 in 2, and SRF-NCOA2 in 1. All fusion positive congenital/infantile SRMS patients with available long term follow-up were alive and well, none developing distant metastases. Among the remaining 15 SRMS patients older than age of one, 10 (67%) showed MYOD1 L122R mutations, most of them following a fatal outcome despite an aggressive multi-modality treatment. All 4 cases harboring co-existing MYOD1/PIK3CA mutations shared sclerosing morphology. All 5 fusion/mutation-negative SRMS cases presented as intra-abdominal or para-testicular lesions.

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Section: Discussionmentioning

confidence: 99%

A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma

Alaggio

Zhang²,

Sung³

et al. 2016

American Journal of Surgical Pathology

217

122

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“…Cardiomyocyte-specific Cited2 knockout mice revealed a requirement specifically in cardiomyocytes with defects in normal myocardial thickening and ventricular septation (32). Furthermore, mutations in Cited2 are associated with congenital heart disease in humans, pointing to an important role for this transcriptional coactivator in cardiac muscle (48,49).…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs in the Myocyte Enhancer Factor 2 (MEF2)-regulated Gtl2-Dio3 Noncoding RNA Locus Promote Cardiomyocyte Proliferation by Targeting the Transcriptional Coactivator Cited2

Clark

Naya

2015

Journal of Biological Chemistry

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Background: MicroRNAs have recently emerged as key regulatory molecules in cardiomyocyte proliferation. Results: miR-410 and miR-495 are regulated by MEF2 in cardiomyocytes, and their overexpression results in increased cardiomyocyte proliferation. Conclusion: miR-410 and miR-495 potently induce cardiomyocyte proliferation by directly inhibiting the coactivator Cited2. Significance: These findings reveal novel microRNAs that can be modulated to stimulate the regeneration of damaged cardiac tissue.

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“…Using the ACMG InterVar classification tool this variant is considered likely benign. Due to conflicting reports in the literature (Xu et al., ), we consider this a variant of unknown significance. Patient 5 had the variant c.926A>G (p.Asn309Ser) found in FOXL1 . FOXL1 is a gene of interest in cardiac defects, particularly hypoplastic left heart, and other congenital anomalies similar to those seen in VACTERL; currently the role of FOXL1 in cardiac defects remains vague (Shaw‐Smith, ).…”

Section: Resultsmentioning

confidence: 99%

“…Using the ACMG InterVar classification tool this variant is considered likely benign. Due to conflicting reports in the literature (Xu et al, 2014), we consider this a variant of unknown significance. (Duffy, Overmann, Keen, Clegg, & Daston, 2004).…”

Section: Genomic Sequencingmentioning

confidence: 99%

Experience with genomic sequencing in pediatric patients with congenital cardiac defects in a large community hospital

Hauser

Solomon²,

Vilboux³

et al. 2018

Molec Gen & Gen Med

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BackgroundCongenital cardiac defects, whether isolated or as part of a larger syndrome, are the most common type of human birth defect occurring on average in about 1% of live births depending on the malformation. As there is an expanding understanding of the underlying molecular mechanisms by which a cardiac defect may occur, there is a need to assess the current rates of diagnosis of cardiac defects by molecular sequencing in a clinical setting.Methods and ResultsIn this report, we evaluated 34 neonatal and pediatric patients born with a cardiac defect and their parents using exomized preexisting whole genome sequencing (WGS) data to model clinically available exon‐based tests. Overall, we identified candidate variants in previously reported cardiac‐related genes in 35% (12/34) of the probands. These include clearly pathogenic variants in two of 34 patients (6%) and variants of uncertain significance in relevant genes in 10 patients (26%), of these latter 10, 2 segregated with clinically apparent findings in the family trios.ConclusionsThese findings suggest that with current knowledge of the proteins underlying CHD, genomic sequencing can identify the underlying genetic etiology in certain patients; however, this technology currently does not have a high enough yield to be of routine clinical use in the screening of pediatric congenital cardiac defects.

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CITED2 Mutation and methylation in children with congenital heart disease

Cited by 42 publications

References 32 publications

A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma

A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma

MicroRNAs in the Myocyte Enhancer Factor 2 (MEF2)-regulated Gtl2-Dio3 Noncoding RNA Locus Promote Cardiomyocyte Proliferation by Targeting the Transcriptional Coactivator Cited2

Experience with genomic sequencing in pediatric patients with congenital cardiac defects in a large community hospital

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