Work

P474: Applying the 2022 guidelines for non-coding variant classification in a large rare disease cohort

Year: 2023

Type: article

Abstract: Recently a patient with ASD and atrial arrhythmia was found to have a microdeletion involving part of MYH6 and MYH7.The authors proposed the potential formation of a hybrid protein, leading to an enhancer at the end of MYH6.Case presentation: Two separate congenital microarray studies that were performed by our laboratory in 2022 identified similar deletions involving portions of MYH6 and MYH7.The first proband is a 24 month old female with developmental delay, where a 19 kb deletion was identified, involving exons 1-20 (of 39 total exons) of MYH6, and exons 38-40 (of 40 total exons) of MYH7.The second proband is a 15 month old male with congenital malfunction of palate, where a 33 kb deletion was identified involving exons 1-20 of the MYH6 gene and exons 16-40 of the MYH7 gene.No additional copy number variants were identified.The microdeletions in both patients were classified as uncertain.Conclusion: While partial deletions of MYH6 and MYH7 have been proposed to form a hybrid MYH6 in a patient with atrial arrhythmia and atrial septal defect, additional studies are necessary to support this assertion and further delineate any associated phenotype.We contribute two additional similar microdeletions in patients with no known cardiac phenotypes [KHMP1] but with separate clinical features and no other genetic findings.It is unknown if formal cardiac evaluation was performed.Given the number of variant types and mechanisms known to be disease causing in MYH7 and the proposed allelic heterogeneity of MYH6, microdeletions partially involving both genes may have clinical impact.

Source: Genetics in Medicine Open

DOI: 10.1016/j.gimo.2023.100521