| Title | Risk of meningomyelocele mediated by the common 22q11.2 deletion. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Vong KIoi, Lee S, Au KSing, T Crowley B, Capra V, Martino J, Haller M, Araújo C, Machado HR, George R, Gerding B, James KN, Stanley V, Jiang N, Alu K, Meave N, Nidhiry AS, Jiwani F, Tang I, Nisal A, Jhamb I, Patel A, Patel A, McEvoy-Venneri J, Barrows C, Shen C, Ha Y-J, Howarth R, Strain M, Ashley-Koch AElizabeth, Azam M, Mumtaz S, Bot GMarkus, Finnell RH, Kibar Z, Marwan AI, Melikishvili G, Meltzer HS, Mutchinick OM, Stevenson DA, Mroczkowski HJ, Ostrander B, Schindewolf E, Moldenhauer J, Zackai EH, Emanuel BS, Garcia-Minaur S, Nowakowska BA, Stevenson RE, Zaki MS, Northrup H, McNamara HK, Aldinger KA, Phelps IG, Deng M, Glass IA, Morrow B, McDonald-McGinn DM, Sanna-Cherchi S, Lamb DJ, Gleeson JG, Koch AElizabeth, Meltzer HS, Le J, Au KSing, Northrup H, Bot GMarkus, Capra V, Finnell RH, Kibar Z, Lupo PJ, Machado HR, Araújo C, Magana T, Marwan AI, Melikishvili G, Mutchinick OM, Stevenson RE, Yurrita A, Zaki MS, Mumtaz S, Medina-Bereciartu JRamón, Kolvenbach CM, Shril S, Hildebrandt F, Noureldeen MM, Salem AMs, Takahashi Y, Salimi-Dafsari H, H Phillips W, Hanak B, Kara B, Güneş ASakarya, Gonda DD, Kirmani S, Tkemaladze T, Gleeson JG |
| Corporate Authors | Spina Bifida Sequencing Consortium‡ |
| Journal | Science |
| Volume | 384 |
| Issue | 6695 |
| Pagination | 584-590 |
| Date Published | 2024 May 03 |
| ISSN | 1095-9203 |
| Keywords | Animals, Chromosome Deletion, Chromosomes, Human, Pair 22, DiGeorge Syndrome, Exome Sequencing, Female, Folic Acid, Folic Acid Deficiency, Humans, Male, Meningomyelocele, Mice, Neural Tube Defects, Penetrance, Spinal Dysraphism |
| Abstract | Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation. |
| DOI | 10.1126/science.adl1624 |
| Alternate Journal | Science |
| PubMed ID | 38696583 |