AUTHOR=Wang Jing , Wang Chunyan , Xie Haiyang , Feng Xiaoyuan , Wei Lei , Wang Binbin , Li Tengyan , Pi Mingan , Gong Li 

TITLE=Case Report: Tetralogy of Fallot in a Chinese Family Caused by a Novel Missense Variant of MYOM2

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.863650

DOI=10.3389/fcvm.2022.863650

ISSN=2297-055X

ABSTRACT=Background: Rare genetic variants have been identified to be important contributors to the risk of Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease (CHD). But relatively limited familial studies with small numbers of TOF cases have been reported to date. Here, we aimed to identify novel pathogenic genes and variants in a Chinese family using whole exome sequencing (WES).
Methods: A Chinese family of the twins with TOF have been recruited in this study.   WES was performed for the affected twins, their healthy brother and parents for recognizing potential pathogenic mutated gene(s). Heterozygous variants carried by the twins, but not the unaffected brother were retained. The public databases were used to assess the frequencies of the selected variants, and the online prediction tools were performed to predict the influences of these variants on protein function. The final candidate variant was further confirmed by Sanger sequencing in other members of the family. 
Results: For several filtering processes, a heterozygous missense variant, in MYOM2 gene (NM_003970.4:c.3097C>T:p.R1033C) was identified and confirmed by Sanger sequencing in the both affected twins and their father, suggesting an inheritance pattern with incomplete penetrance. The variant is extremely rare in the public database. Furthermore, the mutated site was highly conserved among mammals, and as shown using multiple online predict tools, this variant was predicted to be detrimental variant.
Conclusion: We described a family with TOF caused by a rare heterozygous missense variant of MYOM2. Our findings not only further confirm the significant role of genetics in the incidence of TOF but also expand the spectrum of the gene variants that lead to TOF.