Candidate genes and CNVs in VACTERL association
| Chromosome region | Gene | Mutation | Function | Inheritance | Manifestations | Vertebral anomalies | Overlap syndrome | Reference |
|---|---|---|---|---|---|---|---|---|
| 16p13.3 | TRAP1 | p.I253V and p.L525F* | Missense | Homozygous/compound heterozygous | V, A, C, TE, R | Hemivertebrae with rib anomalies | – | Saisawat et al68 |
| 9q21.13 | PCSK5 | p.C1624fs | Frameshift mutation | Heterozygous (inherited-fat) | V, C, R, L | Hemivertebrae | – | Nakamura et al71 |
| 16q24.1-q24.2 | FOXF1 | p.G220C | Missense/deletion | De novo | V, A, C, TE | Butterfly vertebrae | ACD/MPV | Stankiewicz et al;59 Hilger et al45 |
| 1q41 | – | – | Duplication | De novo | V, A, C, TE, R | Butterfly vertebrae | Hilger et al73 | |
| 8q24.3 | – | – | Duplication | De novo | V, A, C TE, R | Butterfly vertebrae | – | Hilger et al73 |
| 13q31.2-qter | – | – | Deletion | De novo | V, A, R, L | Butterfly vertebrae | – | Dworschak et al69 |
| 17p13.3 | – | – | Deletion | NA | V, A, C, L | Butterfly vertebrae | Miller–Dieker syndrome | Ueda et al74 |
| 19q13.2 | DLL3 | p.G269A | Missense | Heterozygous (inherited-mat) | V, C, R, L | Block vertebrae | Spondylocostal dysostosis type I | Giampietro et al67 |
| 13q33.2-qter | – | – | Deletion | De novo | V, A | Block vertebrae | – | Dworschak et al69 |
| 22q11.2 | – | – | Duplication | De novo | V, A, R | Fusion vertebrae (L4–L5) | 22q11.2 duplication syndrome; DiGeorge syndrome | Schramm et al75 |
| Y | – | – | Deletion in Yq and duplication in Yp | NA | V, A, R, L | Block and hemivertebrae in lumbar | – | Bhagat76 |
| 18q10-q11.2 | – | – | Duplication | De novo | V, A, R, L | Dysplastic lumbar and sacral vertebrae, NO detail | – | Felix et al;77 van der Veken et al78 |
| 10q23.31 | PTEN | p.H61D | Missense | De novo | V, C, TE, L | Rib anomalies (13 pairs of ribs) | Cowden syndrome | Reardon et al38 |
| 3q28 | LPP | – | Deletion | De novo | V, C, TE, R | Rib anomalies | – | Arrington et al;39 Hernandez-Garcia et al65 |
| 5q11.2 | – | – | Deletion | De novo | V, A, C | No detail | – | de Jonget al79 |
| 19p13.3 | – | – | Deletion | De novo/inherited-mat | V, A, C, TE, R, L | No detail | – | Peddibhotla et al72 |
| 2q31.1 | HOXD13 | – | Deletion | De novo | A, C, L | Not reported | Brachydactyly-syndactyly syndrome | Garcia-Barcelo et al56 |
| 10q24.32 | FGF8 | p.G29_R34dup; p.P26L | In-frame duplication;missense | Heterozygous | A, C, TE, R, L | Not reported | Kallmann syndrome | Zeidler et al80 |
*Four cases of TRAP1 mutations have been reported and the only case with vertebral anomalies is listed.
A, anal atresia; ACD/MPV, alveolar capillary dysplasia with misalignment of pulmonary veins; C, cardiac malformations; L, limb abnormalities; NA, not available; R, renal anomalies; TE, tracheo-oesophageal fistula; V, vertebral anomalies; VACTERL, vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheo-oesophageal fistula (TE), renal dysplasia (R) and limb abnormalities (L).