日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Congenital heart disease (CHD) is considered to be caused by multifactorial inheritance. Genetic variants and environmental factors have a complex effect on its onset. Chromosomal defects and single-gene disorders can also cause CHD. By analyzing syndromic CHDs and Mendelian inherited familial CHDs, many CHD-related genes have been identified. On the other hand, a large number of CHD-related genes are estimated to be undiscovered. The genetic basis of sporadic CHD also has not been elucidated. Over the last decade, owing to the advances in comprehensive DNA analysis techniques, our understanding of the genetic architecture of CHD is expanding. These advances include next-generation sequencers for nucleotide sequences and chromosomal microarray analysis for copy number abnormalities. Novel CHD-related genes have been reported from comprehensive genetic analyses of rare families and syndromes. Comprehensive genetic analysis of large cohorts have provided new areas of research, such as the identification of genes involved in the development of sporadic CHD and the analysis of epigenetic regulation in CHD development. This article reviews the history and prospects of comprehensive genetic analysis of CHD.