Table 4.
Copy number variations in TS.
| Reference | Sample Size Case/Controls |
Ethnicity | Genotyping Technology | Targeted CNV | Genomewide Finding | Candidate Region | Type of CNV | Frequency | CNV Size | Candidate Gene | CNV Type |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sundaram et al., 2010 [152] | 111/73 | European American | Genomewide SNP chip genotyping | Recurrent or de novo rare exonic CNVs | 5 rare CNVs were found in 10 out of 111 patients with TS. | 3q25.1 | Deletion | 3/111 in cases, 0/73 in controls | 30–40 kb | AADAC | Recurrent |
| 2p16 | Deletion | 2/111 in cases, 0/73 in controls | 230–270 kb | NRXN1 | Recurrent | ||||||
| 10q21 | Deletion | 2/111 in cases, 0/73 in controls | 90–180 kb | CTNNA3 | Recurrent | ||||||
| Chr14 | Deletion | 2/111 in cases, 0/73 in controls | 400–500 kb | FSCB | Recurrent | ||||||
| Chr21 | Duplication | 1/111 in cases, 0/73 in controls | 170–180 kb | KCNE1-KCNE2-RCAN1 | De novo | ||||||
| Fernandez et al., 2012 [150] | 460 (148 trios)/1131 (436 trios) | European | Genomewide SNP genotyping | Rare CNVs (<1%) | 1. No significant increase in the number of de novo or transmitted rare CNVs in cases versus controls; 2. Enrichment of genes within histamine receptor (subtypes 1 and 2) signaling pathways by pathways analyses. | Chr5 | Duplication | 51.8 Mb | 447 RefSeq | De novo | |
| 6p25.3 | Duplication | 316 kb | 1 RefSeq gene | De novo | |||||||
| 20p13 | Deletion | 1.2 Mb | 27 RefSeq genes | De novo | |||||||
| 22q11.21 | Duplication | 2.5 Mb | 56 RefSeq genes | De novo | |||||||
| Nag et al., 2013 [153] | 232/234 | Latin American | Genomewide SNP genotyping | Large CNVs | 1. The rearrangements of COL8A1 and NRXN1 have a nominal significance; 2. Cases with higher large CNV burden: 25/232 in TS; 15/234 in controls (p = 0.006). | 3q12.1 | Duplication | 7/232 in cases, 0/234 in controls p = 0.004 | ~600 kb | COL8A1 | De novo |
| 2p16 | Deletion | 4/232 in cases, 0/234 in controls p = 0.03 | ~400 kb | NRXN1 | De novo | ||||||
| McGrath et al., 2014 [154] | 1086 TS, 1613 OCD/1789 | European | Genomewide SNP genotyping | Large, rare CNVs | Burden of large deletions CNVs previously associated with other neurodevelopmental disorders increased 3.3-fold, whereas no global significant difference in burden of large rare CNVs (p = 0.09). | 16p13.11 | Deletion | 5 cases deletions in 16p13.11 locus, 3 deletions are de novo | >500 kb | De novo | |
| Bertelsen et al., 2016 [155] | 1181/118,730 | European | qPCR or genome-wide genotyping | AADAC deletion | AADAC deletion association test: p = 4.6 × 10−4; OR = 2.1; 95% CI (1.37–3.07). | 3q25.1 | Deletion | 43/1181 (1.82%) in TS cases, 2340/118,730 (0.99%) in controls | ~36 kb | AADAC | Recurrent |
| Huang et al., 2017 [156] | 2434/4093 | European | Genomewide SNP genotyping | Rare CNVs ≥ 30 kb | 1. Enrichment of global CNV burden, for large (>1 Mb), singleton events (OR = 2.28, 95% CI (1.39–3.79), p = 1.2 × 10−3); 2. Enrichment of global CNV burden of known, pathogenic CNVs (OR = 3.03,95% CI (1.85–5.07), p = 1.5 × 10−5); 3. Genome-wide significant loci: (NRXN1 deletions, OR = 20.3, 95% CI (2.6–156.2); CNTN6 duplications, OR = 10.1, 95% CI (2.3–45.4)). | 3p26 | Duplication | 12/2434 (0.49%) in cases, 2/4093 (0.05%) in controls | ~640 kb | CNTN6 | Recurrent |
| 2p16 | Deletion | 12/2434 (0.49%) in cases, 1/4093 (0.02%) in controls | NRXN1 |
CNV: copy number variation.