Significance of α-Myosin Heavy Chain (MYH6) Variants in Hypoplastic Left Heart Syndrome and Related Cardiovascular Diseases. J Cardiovasc Dev Dis 2022 May 03;9(5)
Date
05/28/2022Pubmed ID
35621855Pubmed Central ID
PMC9147009DOI
10.3390/jcdd9050144Scopus ID
2-s2.0-85130146333 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with complex genetic inheritance. HLHS segregates with other left ventricular outflow tract (LVOT) malformations in families, and can present as either an isolated phenotype or as a feature of a larger genetic disorder. The multifactorial etiology of HLHS makes it difficult to interpret the clinical significance of genetic variants. Specific genes have been implicated in HLHS, including rare, predicted damaging MYH6 variants that are present in >10% of HLHS patients, and which have been shown to be associated with decreased transplant-free survival in our previous studies. MYH6 (α-myosin heavy chain, α-MHC) variants have been reported in HLHS and numerous other CHDs, including LVOT malformations, and may provide a genetic link to these disorders. In this paper, we outline the MYH6 variants that have been identified, discuss how bioinformatic and functional studies can inform clinical decision making, and highlight the importance of genetic testing in HLHS.
Author List
Anfinson M, Fitts RH, Lough JW, James JM, Simpson PM, Handler SS, Mitchell ME, Tomita-Mitchell AAuthors
Stephanie S. Handler MD Associate Professor in the Pediatrics department at Medical College of WisconsinJohn W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Michael Edward Mitchell MD Chief, Professor in the Surgery department at Medical College of Wisconsin
