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

Vong K. I., Lee S., Au K. S., Crowley T. B., Capra V., Martino J., ...Daha Fazla

Science, cilt.384, sa.6695, ss.584-590, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 384 Sayı: 6695
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1126/science.adl1624
  • Dergi Adı: Science
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Agricultural & Environmental Science Database, Animal Behavior Abstracts, Applied Science & Technology Source, Aquatic Science & Fisheries Abstracts (ASFA), Artic & Antarctic Regions, ATLA Religion Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Computer & Applied Sciences, EBSCO Education Source, Environment Index, Gender Studies Database, Geobase, Linguistic Bibliography, MEDLINE, Metadex, MLA - Modern Language Association Database, Pollution Abstracts, Psycinfo, Veterinary Science Database, zbMATH, DIALNET, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.584-590
  • Kocaeli Üniversitesi Adresli: Evet

Özet

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.