Table 3.
Genomic structural aberrations in TS.
| Cytoband | Variation Type | Karyotype | Carrier Frequency and Phenotype | Candidate Region | Candidate Gene | Reference |
|---|---|---|---|---|---|---|
| 6q16 | Translocation and deletion | 46, XY, balanced t(6;22)(q16.2;p13) | One family, 2 carriers of translocation + deletion: proband with TS + OCD; mother with OCD | A 400 kb deletion, 1.3 Mb telomeric to the translocation breakpoint, was also identified on 6q16. | GPR63, NDUFA4, and KLHL32 in the 400 kb deletion on 6q16 | [127] |
| 7q22–q31 | Translocation | 46, XY, t(7;18)(q22;q22.3) | One pedigree with 12 individuals; 9 carriers: 4 with vocal tics; 1 with motor tics; 1 with TS, 3 without TS | Breakpoint at 7q22 was localized between markers D7S515 and D7S522. | IMMP2L | [45] |
| Duplication/Insertion | 46, XY, dup(7)(q22.1–q31.1) | 1 patient with TS + depression + delayed speech + mental retardation | Breakpoint on chr7 was mapped to 7q22–q31, between D7S515 and D7S552, 6.5 kb. | IMMP2L | [46,128] | |
| Translocation and deletion | 46, XY, t(2;7)(p24.2;q31)del(7)(q31.1q31.2) | 1 TS patient with motor tics + language impairment | Translocation breakpoint on chr7 was mapped to 7q31. A 7.25 Mb deletion within introns 2–3 on 7q31.1–31.2 was identified. | IMMP2L | [122] | |
| Deletion | Intragenic deletion | 188 TS patients and 316 controls: 7 out of 188 TS; 3 out of 316 controls carried the deletion (p = 0.0047) | 49~331 kb deletions were identified at the 5’end of IMMP2L gene. | IMMP2L | [123] | |
| 7q35–q36 | Complex chromosomal insertion/translocation | Father: 46, XY, inv(2)(p23q22), ins(7;2)(q35q36;p21p23); Daughter and son: 46, XX/XY, der(7)ins(7;2)(q35q36;p21p23) | One family with 3 carriers: daughter and son with TS + OCD; father with OCD + depression | a chromosome 2p21–p23 insertion on chromosome 7q35–q36, interrupting the contactin-associated protein 2 gene (CNTNAP2). | CNTNAP2 | [124] |
| Translocation | Proband and aunt: 46, XY/XX, der(7)t(7;15)(q35;q26.2) | One large family with 5 carriers: 2 (proband and aunt) with multiple congenital malformations, severe mental retardation and did not have any language development, and scoliosis. Father, grandmother, father of grandmother: 46, XY/XX, balanced t(7;15)(q35;q26.2) without TS and other malformations | Breakpoint localized to a region of approximately 21 kb within intron 11 of the CNTNAP2 gene; and carriers without TS. | CNTNAP2 | [125] | |
| 8q13–q22 | Translocation | 46, XY, t(6;8)(p23;q13) | One family with 3 carriers: proband with TS + OCD + LD; half-sister with TS + OCD; mother with LD + TS?; One family with 1 carrier: with TS + ADHD | Breakpoint within 8q13. | Unknown | [129] |
| Translocation | 46, XY, t(1;8)(q21.1;q22.1) | 4 carriers in one family, 1 without TS; 1 with TS + ADHD + OCD, 2 with motor tics + ADHD | Breakpoint within 8q22. | CBFA2T1 located 11 kb distal to the 8q breakpoint | [130] | |
| 9p | Deletion | 46, XY, del(9)(qter—p2304:) | One patient with TS + OCD + ADD | Breakpoint lies on chr9. | Unknown | [131] |
| Translocation | 46, XY, t(3;9)(q25.1;q34.3) | 1/176 TS cases | Breakpoint on chr9q34.4 within intron7 of OLFM1 gene. | OLFM1 | [132] | |
| Translocation | 46, XX/XY, t (3;9) (q25.1;q34.3) | One family with 2 carriers with TS | Unknown | Unknown | [132] | |
| 13q | Var321, inversion | 46, XY, inv(13)(q31.1;q33.1) | 1/174 TS patients: with TS+ADHD; 2 patients carried var321 | Breakpoint spans the 13q31.1 and 13q33.1. | SLITRK1, ERCC5 and SLC10A2 | [51] |
| Var321, inversion | 46, XY, inv(13)(q31.1;q33.1) | 2/174 TS patients carried var321, none of 2148 controls carried var321 (p = 0.0056) | Breakpoint spans the 13q31.1 and 13q33.1. | SLITRK1, ERCC5 and SLC10A2 | [133] | |
| 15q13.3; Xq21.31 | Microduplication and deletion | Deletion in 15q13.2, duplication in both 15q13.3 and Xq21.31 | One family with 2 carriers: proband with TS + OCD + rage attack; mother with ADHD | Breakpoint within 15q13.2, 15q13.3 and Xq21.31 (2-bp deletion at 15q13.2; 433 kb duplication at 15q13.3; 732 kb duplication at Xq21.31). | CHRNA7, PABPC5 and PCDH11X | [134] |
| 15q13–q22.3 | Inversion | 46, XY, inv(15)(q13;q22.3) | One family with 1 carrier: proband with motor tics + ADHD + OCD + development delay | Inversion spans 15q13–q22. | Unknown | [135] |
| 16q22–q23 | Fragile sites | 46, XX/XY, fr(16)(q22–23) | 3/281 carriers: one with TS + Huntington’s Disease; one with TS + BPD + ASD + MR; one with TS + BPD + MR | Fragile site lies within 16q22–q23. | Unknown | [136] |
| 17p11 | Translocation | 46, XY, t(6;17)(q21;p11) | One family with 2 carriers: proband with TS; son with TS + LD | Breakpoint lies within 17p11. | Unknown | [137] |
| Deletion | 46, XY, del(17)(p11.2) | One patient with TS + SMS + SIB + ADHD + OCB | Unknown | [138] | ||
| 18q21.1–q22.3 | Translocation | 46, XX, t(2;18)(p12;q22) | One patient with OCD | Breakpoint lies within 18q. | CDH7 and CDH19 | [139] |
| 18q21.1–q22.2 | Inversion | 46, XY, inv(18)(q21;q22) | One patient with tics + OCD | Breakpoint lies at 18q, the inverted chromosome showing delayed replication timing. | 2 transcripts, GTSCR-1 and CIS4 | [140] |
| 22q11 | Deletion | 46, XX, del(22)(q11) | One family with 2 carriers: proband with TS + ADHD + OCD + MR; mother with phonic tic | A deletion at 22q11. | Unknown | [141] |
| Xp22.3 | Deletion | 46, XY | One family with 3 carriers: proband with TS + ASD; brother with TS + ADHD, mother without TS, but with depression + anxiety + learning disability | A small deletion encompassing exons 4, 5, and 6 of NLGN4 at Xp22.3. | NLGN4 | [126] |
LD: learning disorder; ADD: attention deficit disorder; MR: mental retardation; SMS: Smith-Magenis syndrome; SIB: self injurious behavior; OCB: obsessive compulsive behavior.