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Catalog
2023 ACMG Annual Clinical Genetics Meeting Digital ...
Variants in
MED12
are Associated with Lef ...
Variants in
MED12
are Associated with Left Ventricular Non-Compaction and Arrhythmia
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Pdf Summary
A recent study published in JCI Insight by Baskin et al. (2017) has shown that MED12, a mediator complex subunit involved in transcription regulation, plays a role in the regulation of calcium-handling genes in the heart. In this study, they observed that mice with cardiomyocyte-specific Med12 deletion exhibited altered calcium handling and dilated cardiomyopathy (DCM). <br /><br />Building on this knowledge, Li et al. (2020) identified de novo loss-of-function variants in MED12 in females with Hardikar syndrome (HS), a combination of multi-systemic birth defects with normal intellectual development. They found that these variants were associated with left ventricular non-compaction (LVNC), a form of DCM, in some of the patients. <br /><br />In another study by Polla et al. (2020), de novo variants in MED12 were found in females with X-linked syndromic neurodevelopmental disorders. Again, LVNC was observed in some of these patients. <br /><br />Based on these findings, the researchers propose that females with MED12 phenotypes, such as HS or X-linked intellectual disability (XLID), may be at risk for LVNC, which could progress to dilated cardiomyopathy. They also suggest that these females may be susceptible to ventricular fibrillation, even in the absence of left ventricular dysfunction. <br /><br />The study presented a case series of six females with pathogenic variants in MED12, all of whom exhibited LVNC, dilated cardiomyopathy, or arrhythmia. It was noted that patients with missense variants had more severe cardiac dysfunction compared to those with splice variants. However, one patient with a missense variant required a heart transplant, while another with a missense variant improved after surgical correction of septal defects. <br /><br />The study highlights the need for further development of strategies to assess ongoing arrhythmogenic risk in these patients, in addition to ambulatory heart rhythm monitoring. <br /><br />In conclusion, this case series adds to the growing evidence of an association between MED12 variants and cardiac phenotypes, specifically LVNC and arrhythmia. The findings suggest that females with MED12-associated phenotypes may be at risk for these cardiac conditions and require close monitoring and intervention.
Asset Subtitle
Presenting Author - Nicole Weaver, MD; Co-Author - Amy Shikany, MS, LGC; Co-Author - Emile Vieta, M.D.; Co-Author - Bianca E. Russell, MD; Co-Author - Bruce B. Lerman, MD; Co-Author - Alanna Strong, MD; Co-Author - Dong Li, PhD;
Meta Tag
Cardiac/circulatory disorders
Cardiovascular System
Natural History
Co-Author
Amy Shikany, MS, LGC
Co-Author
Emile Vieta, M.D.
Co-Author
Bianca E. Russell, MD
Co-Author
Bruce B. Lerman, MD
Co-Author
Alanna Strong, MD
Co-Author
Dong Li, PhD
Presenting Author
Nicole Weaver, MD
Keywords
MED12
transcription regulation
calcium-handling genes
heart
cardiomyocyte-specific Med12 deletion
calcium handling
dilated cardiomyopathy
Hardikar syndrome
left ventricular non-compaction
X-linked syndromic neurodevelopmental disorders
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