Table 1.
Genomic hotspot rearrangements and their associated phenotypes
| Locus | Del or dup | Coordinates (Build 36) and size of critical region | Associated phenotypes | Possible candidate genes | Size and % sequence identity of flanking repeats | References |
|---|---|---|---|---|---|---|
| 1q21.1 | del | chr1: 144.10–144.60 Mb 500 kb | TAR syndrome: hypomegakaryocytic thrombocytopenia, upper extremity abnormalities ranging from bilateral absent radii to phocomelia; normal intellect | PIAS3, Lix1L | 19 kb >95.0% | [27] |
| 1q21.1 | del | chr1: 145.0–146.35 1.35 Mb | Deletion: variable phenotypes: two groups report mild to severe MR, microcephaly, occasional congenital heart disease; two studies find enrichment of the deletion in schizophrenia | GJA5, GJA8, HYDIN2 | 281 kb >99.9% | [30,31,51–53] |
| dup | Duplication: macrocephaly, mild to moderate delays, autistic features; unlike the deletion, has not been seen in schizophrenia | |||||
| 3q29 | del | Chr3: 197.4–198.9 1.5 Mb | Deletion: mild to moderate MR, microcephaly, mild dysmorphic features | PAK2, DLG3 | 21 kb >97.1% | [46–48] |
| dup | Duplication: mild to moderate MR | |||||
| 10q22–q23 | del | Chr10: 81.12–89.07 Mb 7.95 Mb | Two families reported: deletion carriers have cognitive and behavioral abnormalities of varying severity including: learning disabilities, speech and language delay, mild developmental delays | NRG3, GRID1, BMPR1, ASNCG, GLUD1 | 107 kb >98% | [41] |
| 15q13.3 | del | Chr15: 28.7–30.2 Mb 1.5 Mb | Deletion: variable phenotypes - mild to severe MR, mild dysmorphism, digital abnormalities, autism; schizophrenia; IGE | CHRNA7 | 218 kb >99.4% | [18,30,31,54–57] |
| dup | Duplication: few patients reported, mild to moderate delays; unlike deletion of the same region, has not been reported in schizophrenia or IGE | |||||
| 15q24 | del | Chr15: 72.2–73.8 Mb 1.8 Mb | Mild to moderate MR, high anterior hairline, downslanting PF, long philtrum, digital abnormalities, genital abnormalities, loose connective tissue | MAN2C1, CYP11A1, STRA6 | 51 kb >94.0% | [38,39] |
| 16p13.11 | del | chr16:15.4–16.4 Mb | Deletion: MR, autism, brain abnormalities | NDE1, NTAN | 138 kb >99.0% | [49,50] |
| dup | 1 Mb | Duplication: autism, MR; decreased penetrance | ||||
| 16p11.2 | del | chr16: 29.50–30.10 Mb 600 Kb | Deletion: detected in 0.5–1% of individuals with autism; also seen in 0.1% of individuals with psychiatric or language disorders, 0.01% of controls | MAPK3, MAZ, DOC2A, SEZ6L2, HIRIP3 | 146 kb >99.4% | [21,25] |
| dup | Duplication: autism, psychiatric or language disorders (0.04%); also seen in 0.03% of population controls | |||||
| 16p11.2–p12.2 | del | chr16: 22.0–28.0 Mb 6 Mb | Severe developmental delay; hypotonia; flat facies, downslanting palpebral fissures, posteriorly rotated ears | Many genes | 146 kb >99.4% | [40] |
| 17q12 | del | Chr17: 31.8–33.3 Mb 1.5 Mb | Deletion: Renal abnormalities ranging from severe multicystic dysplastic kidneys to occasional renal cysts; renal cysts and diabetes (RCAD) syndrome | HNF1B | 76 kb >99% | [28] |
| 17q21.31 | del | chr17: 41.0–41.7 Mb 700 kb | Mild to severe global developmental delay, childhood hypotonia, long face, tubular or pear-shaped nose, bulbous nasal tip, friendly/amiable behavior | MAPT, CRHR1 | 38 kb >98% | [15,18,19,34] |
| Distal 22q11.2 | del | chr22:19.8–22.0 Mb 2.2 Mb | Deletion: prematurity, growth delay, learning problems and/or developmental delay, various skeletal abnormalities | MAPK1 | 10 kb >95.9% | [44,45] |
| dup | Duplication: mild to moderate MR, mild dysmorphic features | |||||