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Publication : Risk of meningomyelocele mediated by the common 22q11.2 deletion.

First Author  Vong KI Year  2024
Journal  Science Volume  384
Issue  6695 Pages  584-590
PubMed ID  38696583 Mgi Jnum  J:348704
Mgi Id  MGI:7643269 Doi  10.1126/science.adl1624
Citation  Vong KI, et al. (2024) Risk of meningomyelocele mediated by the common 22q11.2 deletion. Science 384(6695):584-590
abstractText  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.
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