Table 2.
Duplications of upstream and downstream SHOX CNEs and their phenotypes - literature data (IUGR-intrauterine growth retardation, NA – not available)
| Author, year | SHOX and SHOX-area duplication size and localization | Methodology | Clinical phenotype | X Ray | ||
|---|---|---|---|---|---|---|
| Type | Localization | Size | ||||
| Iughetti, 2010 (39) | dup | exon 1 SHOX gene to enhancer | 500 kb | MLPA | ISS | Normal |
| Benito-Sanz, 2011 (20) | dup | SHOX gene 5’ region | MLPA | ISS | Normal | |
| Caliebe, 2012 (32) | dup | 647,566–915,079 bp | 267.5 kb | MLPA | IUGR; microcephaly, SS | NA |
| dup | Xp22.33 (779,805–915,079 bp); 239.4 kb proximal of SHOX | 135.3 kb | MLPA | ISS | NA | |
| Hirschfeldova, 2012 (40) | dup | CNE9 | MLPA, SHOX sequencing | LWD – proportional short stature, (-2.5 SD), short forearm, cubitus valgus, and muscular hypertrophy | NA | |
| Sandoval, 2014 (34) | dup | CNE9 | MLPA, aCGH | ISS, disproportionate | NA | |
| Fukami, 2015 (16) | dup | CNE-2 (upstream). Exons 1-6b, CNE4, CNE5 (downstream) | MLPA | ISS | Normal | |
| dup | Exons 1-6b, CNE4, CNE5, ECR1 and CNE9/ECS4 (downstream) | MLPA | ISS | Normal | ||
| dup | CNE-2, CNE-3, CNE-5 (upstream), Exons 1-3 | MLPA | ISS | Normal | ||
| dup | CNE9 | MLPA | ISS | Normal | ||
| Bunyan, 2016 (36) | dup | CNE2, CNE3, CNE4, CNE5, CNE6, ECR1,CNE8, ECS4(CNE9) and possibly X:970,000 | MLPA, aCGH | Short stature, LWD, Disproportionate limbs | bilateral Madelung deformity | |
| dup | CNE8, ECS4 (CNE9) and X:970,000 | Short stature, LWD – Disproportionate limbs | bilateral Madelung deformity | |||
| dup | CNE8, ECS4 (CNE9) and X:970,000 | Short stature, LWD Disproportionate limbs, bowing of forearms | bilateral Madelung deformity | |||
| dup | ECS4 (CNE9) X:821,993-961,522 (hg19) | 113-140 kb | ISS; short stature | Normal | ||
| dup | X:970,000 (and possibly affects ECS4) | Short stature, LWD Mesomelia | bilateral Madelung deformity | |||
| dup | CNE-3, CNE-2 | Short stature, LWD | Bilateral Madelung deformity | |||
| Shima, 2016 (37) | dup | SHOX Exons 1–3 and upstream CNE-5, CNE-3, and CNE-2 | ISS | Normal | ||
| dup | Entire SHOX gene and upstream CNE-2, downstream CNE4 and CNE5 | ISS | Normal | |||
| dup | Entire SHOX gene and downstream CNE4, CNE5, ECR1 and CNE9/ECS4 | ISS | Normal | |||
| dup | CNE9 | ISS | Normal | |||
| dup | Downstream region | ISS | Normal | |||
| Hirschfeldova, 2017 (35) | dup | Large dup SHOX gene and downstream regulatory elements | MLPA | ISS | Normal | |
| dup | CNE9 (different sizes) | MLPA | ISS | Normal | ||
| dup | Large dup Intron 6 SHOX gene, CNE3, 4, 5, 7, 8, 9 | MLPA | ISS | Normal | ||
| dup | Large dup CNE4, 5, 7, 8, 9 | MLPA | ISS | Normal | ||
| dup | CNE-2, CNE-5 (upstream) | MLPA | ISS | Normal | ||
| Capkova, 2020 (41) | dup | Downstream regulatory elements, not detailed | MLPA, FISH, Sanger Sequencing | ISS | Normal | |
| Fanelli A, 2022 (38) | dup | chrX:917,600 - 1,030,000 | aCGH and breakpoint PCR | LWD | Normal | |