Table 2.

Exome and whole genome sequencing for cardiovascular disease gene identification.

Disease	Inheritance model	Sequenced subjects	Putative loci identified	Validation	Reference
Complex I deficiency with hypertrophic cardiomyopathy	Autosomal recessive	One proband	ACAD9	Wild-type cDNA complementation in fibroblasts; compound heterozygous or homozygous mutations found in ACAD9 in 120 index cases with complex I deficiency	54
Dilated cardiomyopathy	Autosomal dominant	Four affected family members	BAG3	7 structural and single- nucleotide variants found in BAG3 in 311 unrelated probands; knockdown of bag3 in zebrafish recapitulated the phenotype	35
Familial thoracic aortic aneurysm	Autosomal dominant	Two distantly- related affected individuals in one family	SMAD3	Cosegregation in family; sequencing of 181 additional probands identified three additional SMAD3 mutations in four families	53
Infantile mitochondrial cardiomyopathy	Autosomal recessive	One proband	AARS2	Co-segregation of mutation in a separate family; metabolomic analysis of post-mortem heart and skeletal muscle of proband demonstrating increased alanine levels	55
Kabuki syndrome	Autosomal dominant	Ten unrelated cases	MLL2	Sanger sequencing confirmation in 26 of 43 additional cases	56
Moyamoya disease	Complex	Index case from each of eight families	RNF213	Genome wide linkage analysis; combination of linkage analysis and sequencing of RNF213 in 42 index cases; case-control study in 958 subjects of East Asian ancestry	57
Sick sinus syndrome (SSS)	Complex	7 individuals with SSS and the rs28730774[T] variant associated with SSS; 80 individuals without SSS	MYH6	Genotyping in 469 SSS cases and 1185 controls	58