Research: Human Genetics of Ventricular Septal Defect

Adv Exp Med Biol

. 2024:1441:505-534.

 doi: 10.1007/978-3-031-44087-8_27.

Human Genetics of Ventricular Septal Defect

Andreas Perrot 1Silke Rickert-Sperling 2

Affiliations expand


Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.

Keywords: 22q11 deletion syndrome; ACP6; ACTC1; ADCY2; ASD; Adams–Oliver syndrome; Alagille syndrome; Atrial septal defect; B3GALTL; BCL9; BCOR; Blepharophimosis syndrome; Brugada syndrome; CACNA1D; CACNA1F; CACNA1S; CFC1; CHARGE syndrome; CHD1; CHD7; CITED2; CNV; CRKL; CRYPTIC; Char syndrome; Copy number variation; Cornelia de Lange syndrome; Costello syndrome; Cri-du-chat syndrome; DVL1; DiGeorge syndrome; Diaphragmatic hernia; Down syndrome; EVC1; EVC2; Edwards syndrome; Ellis–van Creveld syndrome; FBN1; FGFR3; FMO5; FOXL2; Frank–ter Haar syndrome; GATA4GATA binding protein (GATA)GATA4; GATA6; GDF3Growth differentiation factor (GDF)GDF3; GJA5; GPC3; GWAS; HAS2; HEY2; HRAS; Holt–Oram syndrome; Hypophosphatemia; IRX4; ISL1; JAG1; Jacobsen syndrome; KMT2A; Kabuki syndrome; Kleefstra syndrome; LBR; LVNC; Larsen-like syndrome; MAML3; MEIS2; MESP1; MID1; MKRN2; MLL2; MYBPC3; MYH6; MYH7; Marfan syndrome; Mowat–Wilson syndrome; Muenke syndrome; NF1; NIPBL; NKX2-5; NKX2-6; NOTCH1; NOTCH2; NSD1; NTRK3; Neurofibromatosis; Nodal; Noncompaction; Noonan syndrome; Noonan-like syndrome; Oculofaciocardiodental syndrome; Okihiro syndrome; Opitz syndrome; PITX2; PLCB2; PRKAB2; PTPN11; Pallister–Killian syndrome; Patau syndrome; Pelger–Huet anomaly; Peters plus syndrome; Potocki–Lupski syndrome; ROR2; Ras/MAPK; Robinow syndrome; SALL1; SALL4; SCN5A; SH3PXD2B; SHOC2; SMAD2; SOX7; Simpson–Golabi–Behmel syndrome; Sotos syndrome; TBX1; TBX15; TBX20T-box (TBX)TBX20; TBX3; TBX5; TDGF1; TFAP2B; TGFβTransforming growth factors (TGFs)TGFß; TNNI3; Townes–Brock syndrome; Trisomy 13; Trisomy 18; Trisomy 21; Ulnar–mammary syndrome; VSD; Velocardiofacial syndrome; Ventricular septal defect; Ventricular septum; WES; WNT5A; Whole exome sequencing; Williams–Beuren syndrome; Wolf–Hirschhorn syndrome; ZFHX1B; ZIC3.

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