Table 2.
Microdeletion and microduplication syndromes with genomic copy number variation and CHD
| Syndrome | Chromosome region | Frequency of CHD among patients (%) | CHD candidate gene(s) in regiona | Function of candidate gene(s)e | Reference (OMIM #) |
|---|---|---|---|---|---|
| Microdeletion syndromes | |||||
| 8p23.1 deletion syndrome | 8p23.1 | 94 | GATA4 | GATA-binding TF | [195] |
| 17q23 microdeletion syndrome | 17q23 | 86 | TBX2 | T-box TF | [216] (613355) |
| DiGeorge syndrome | 22q11.2 | 65–75 | TBX1; CRKL | T-box TF; Tyrosine kinase | [263] (188400) |
| 1p36 deletion syndrome | 1p36 | 71 | DVL1 | WNT signaling component | [264] (607872) |
| 2q31.1 microdeletion syndrome | 2q31.1 | 70 | SP3 | Sp TF | [265] |
| Kleefstra syndrome | 9q34 | 40 | EHMT1 | H3K9 methyl transferase | [205, 206, 208] (610253) |
| 16p12.2–p11.2 microdeletion syndrome | 16p12.2–p11.2 | 60 | N/A | [266] (613604) | |
| Jacobsen syndrome | 11q23-qter | 56 | N/A | [267] (147791) | |
| Wolf–Hirschhorn syndrome | 4p16.3 | 50 | WHSC1; FGFRL1 | H3K36 methyl transferase; fibroblast growth factor receptor | [268] (194190) |
| Williams–Beuren Syndrome | 7q11.23 | 53–85 | ELN; BAZ1B | Elastin; subunit of chromatin remodeling complex | [180] (194050) |
| Smith–Magenis syndrome | 17p11.2 | 40–45 | MAPK7 b | MAP kinase | [269, 270] (182290) |
| Koolen-De Vries syndrome | 17q21.31 | 27–36 | KANSL1 c | Subunit of NSL histone acetylation complex | [210, 212] (610443) |
| 1q21.1 deletion syndrome | 1q21 | 29 | GJA5 | Connexin 40 | [197, 271] |
| Miller–Dieker lissencephaly syndrome | 17p13.3 | 22 | N/Ad | [272, 273] (247200) | |
| Sotos syndrome | 5q35 | 21 | NSD1 | H3K36 methyl transferase | [274–276] (117550) |
| Brachydactyly-mental retardation syndrome | 2q37 | 20 | HDAC4 | Histone deacetylase | [277, 278] (600430) |
| 15q13 microdeletion syndrome | 15q13 | 15 | N/A | [279, 280] (612001) | |
| Microduplication syndromes | |||||
| 16p13.3 microduplication | 16p13.3 | 40 | CREBBP | Histone acetyltransferase | [281] (613458) |
| 16p13.11 microduplication | 16p13.11 | 20 | MYH11 | Smooth muscle myosin HC | [282] |
| Potocki–Lupski syndrome | 17p11.2 | 50 | MAPK7 | MAP kinase | [283, 284] (610883) |
| 22q11.2 duplication syndrome | 22q11.2 | 15 | TBX1 | T-box TF | [285] (608363) |
| Chromosomal aneuploidy | |||||
| Patau syndrome | 47, +13 (trisomy 13) | 86 | N/A | [150] | |
| Edward syndrome | 47, +18 (trisomy 18) | 61–94 | N/A | [147, 148] | |
| Down syndrome | 47, +21 (trisomy 21) | 50 | N/A | [146] (190685) | |
aGenes causing heart defects when deleted in mice (http://www.informatics.jax.org) (bold) and/or by point mutations in additional patients with CHD as part of the clinical spectrum (underlined)
bPoint mutations in RAI1 causes Smith–Magenis syndrome, but CHD have not been reported in patients with point mutations in RAI1 and cardiac defects are not observed in the Rai1 mouse model [286]
cOne out of four KDVS patients with point mutations in KANSL1 had CHD
dThe lissencephaly phenotype of MDLS is caused by haploinsufficiency of the PAFAH1B1 gene (also known as LIS1) [287, 288], but it is presently unknown which gene is responsible for heart defects in MDLS patients
e TF transcription factor