Table 2 Examples of noncoding structural variants (SVs) putatively causal in neurodevelopmental disorders (NDDs).
From: Interpreting the impact of noncoding structural variation in neurodevelopmental disorders
Locus | Affected genea | SV type | Noncoding disease mechanism | NDD phenotype | Reference |
|---|---|---|---|---|---|
lncRNAs | |||||
22q11.2 | DGCR5 | Translocation, deletion | DGCR5 haploinsufficiency | DiGeorge syndrome; SCZ | |
5q15 | lnc-NR2F1 | Translocation, deletion | lnc-NR2F1 haploinsufficiency | DD, facial dysmorphisms, hearing loss | |
Xp22.11 | PTCHD1-AS | Deletion | PTCHD1-AS haploinsufficiency | ASD | |
14q21.1 | lncLRFN5-10 | Deletion | LRFN5 haploinsufficiency | ASD | |
2p25.1 | LINC00299 | Translocation, deletion | LINC00299 haploinsufficiency | DD, ID | |
12q23.1 | RMST | Translocation | RMST haploinsufficiency | Kallmann syndrome | |
14q32.2 | MEG3 | Deletion (maternal) | MEG haploinsufficiency | upd(14)pat phenotype | |
15q11-13 | SNORD116 | Deletion | snoRNA haploinsufficiency | Prader–Willi syndrome | |
Near cis-regulatory elements (promoter and 5’&3’ UTR) | |||||
Xq27.3 | FMR1 | CGG repeat expansion | Promoter hypermethylation | Fragile X syndrome | |
16p12.3 | XYLT1 | GGC repeat expansion | Exon 1 hypermethylation | Baratela–Scott syndrome | |
Xq28 | AFF2 | CCG repeat expansion | Promoter hypermethylation | ID | |
2q11.2 | AFF3 | CGG repeat expansion | Promoter hypermethylation | ID | |
12q13.1 | DIP2B | CGG repeat expansion | Promoter hypermethylation | ID | |
16q21 | GPR56 | Deletion | Promoter TFBS disruption | Polymicrogyria, ID, speech delay, seizures | |
Intergenic regulatory elements and 3D chromatin conformation | |||||
7q36.3 | SHH | Translocation | Enhancer displacement | Holoprosencephaly | |
14q12 | FOXG1 | Translocation, deletion | Enhancer displacement/removal or 3D reorganization | Congenital Rett syndrome | |
5q14.3 | MEF2C | Translocation, deletion, inversion | Enhancer displacement/removal | Rett-like syndrome | |
2q33.1 | SATB2 | Translocation, inversion | Enhancer displacement | Glass syndrome | |
17q24.3 | SOX9 | Translocation, deletion duplication | Enhancer displacement/removal, Enhancer adoption | Pierre Robin sequence Cooks syndrome, sex reversal | |
Xq27.1 | SOX3 | Insertion, deletion | Enhancer insertion/removal | Variable phenotypes | |
7q21.3 | DLX5/6 | Translocation, deletion, inversion | Enhancer displacement/removal | SHFM1, ID, craniofacial defects, hearing loss | |
4q25 | PITX2 | Translocation, deletion | Enhancer displacement/removal | Rieger syndrome | |
11p13 | PAX6 | Translocation | Enhancer displacement | Aniridia | |
Xp21.3 | ARX | Duplication | Enhancer duplication | ID, epilepsy, lissencephaly | |
6p24.3 | TFAP2A | Translocation, inversion | Enhancer displacement, 3D reorganization | BOFS | |
14q32.2 | BCL11B | Translocation | Enhancer removal | DD, speech delay, ID | |
1p34.2 | SLC2A1 | Translocation | Enhancer displacement | Epilepsy, DD | |
7q36.3 | VIPR2 | Duplication | Unknown | SCZ | |
15q26.2 | NR2F2 | Duplication | Enhancer duplication | ASD, ID | |
21q22.2 | DSCAM | Intronic deletion | Enhancer removal | ASD | |
2p12 | CTNNA2 | Translocation | Enhancer displacement | ID, DD | |
