2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Potential Clinical Significance of Microdeletions involving both MYH6 and MYH7

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From 2012 to 2022, six partial deletions and six partial duplications of the MYH6/MYH7 region have been identified. Two of the deletions were reported to have a cardiac phenotype, but no cardiomyopathy, and one of these individuals also had trisomy 21. Four of the deletions were inherited, while the inheritance of two is unknown. Two of the duplication cases reported a cardiac phenotype, and two had unknown inheritance. The majority of these deletions and duplications have identical breakpoints by microarray, suggesting a recurrent deletion/duplication mechanism.<br /><br />Missense variants in MYH6 are associated with cardiomyopathy, atrial septal defect, and other cardiac phenotypes. Gain-of-function variants in MYH7 cause hypertrophic cardiomyopathy, while variants leading to reduced function result in dilated cardiomyopathy. Haploinsufficiency is not thought to result in disease for either gene.<br /><br />In one reported case, a patient had a maternally inherited deletion involving part of MYH6 and MYH7. This deletion resulted in a hybrid MYH6 protein with reduced function. For partial duplications, it is unknown if they would disrupt gene function or if there would be a resulting cardiac phenotype if gene function was lost.<br /><br />A table provides details of patients with partial deletions or duplications of MYH6/MYH7, including additional microarray findings and phenotypes. However, there is no established disease correlation for these deletions and duplications at present. The reported phenotypes are inconsistent, and some of the cases have been inherited from reportedly asymptomatic individuals. More cases are needed for a definitive genotype/phenotype correlation.

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Presenting Author - McKinsey Goodenberger, MS, CGC; Co-Author - Nicole L. Hoppman, PhD; Co-Author - Hutton M. Kearney, PhD; Co-Author - Kristen J. Rasmussen, MS, CGC;

Meta Tag

array CGH

Cardiovascular System

Genetic Testing

Co-Author Nicole L. Hoppman, PhD

Co-Author Hutton M. Kearney, PhD

Co-Author Kristen J. Rasmussen, MS, CGC

Presenting Author McKinsey Goodenberger, MS, CGC

Keywords

partial deletions

partial duplications

MYH6/MYH7 region

cardiac phenotype

trisomy 21

inherited

microarray breakpoints

recurrent deletion/duplication mechanism

missense variants

cardiomyopathy