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Risk of meningomyelocele mediated by the common 22q11.2 deletion.
Vong, Keng Ioi; Lee, Sangmoon; Au, Kit Sing; Crowley, T Blaine; Capra, Valeria; Martino, Jeremiah; Haller, Meade; Araújo, Camila; Machado, Hélio R; George, Renee; Gerding, Bryn; James, Kiely N; Stanley, Valentina; Jiang, Nan; Alu, Kameron; Meave, Naomi; Nidhiry, Anna S; Jiwani, Fiza; Tang, Isaac; Nisal, Ashna; Jhamb, Ishani; Patel, Arzoo; Patel, Aakash; McEvoy-Venneri, Jennifer; Barrows, Chelsea; Shen, Celina; Ha, Yoo-Jin; Howarth, Robyn; Strain, Madison; Ashley-Koch, Allison Elizabeth; Azam, Matloob; Mumtaz, Sara; Bot, Gyang Markus; Finnell, Richard H; Kibar, Zoha; Marwan, Ahmed I; Melikishvili, Gia; Meltzer, Hal S; Mutchinick, Osvaldo M; Stevenson, David A; Mroczkowski, Henry J; Ostrander, Betsy; Schindewolf, Erica; Moldenhauer, Julie; Zackai, Elaine H; Emanuel, Beverly S; Garcia-Minaur, Sixto; Nowakowska, Beata A; Stevenson, Roger E; Zaki, Maha S.
Afiliação
  • Vong KI; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Lee S; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Au KS; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Crowley TB; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Capra V; Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children's Memorial Hermann Hospital, Houston, TX 77030, USA.
  • Martino J; 22q and You Center, Division of Human Genetics, Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Haller M; Genomics and Clinical Genetics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
  • Araújo C; Division of Nephrology, Department of Medicine, Columbia University, NY 10027, USA.
  • Machado HR; Center for Reproductive Medicine, Department of Molecular and Cellular Biology and Scott Department of Urology, Baylor College of Medicine, TX 77030, USA.
  • George R; Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14040-900, Brazil.
  • Gerding B; Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14040-900, Brazil.
  • James KN; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Stanley V; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Jiang N; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Alu K; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Meave N; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Nidhiry AS; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Jiwani F; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Tang I; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Nisal A; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Jhamb I; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Patel A; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Patel A; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • McEvoy-Venneri J; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Barrows C; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Shen C; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Ha YJ; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Howarth R; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Strain M; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ashley-Koch AE; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Azam M; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Mumtaz S; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Bot GM; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Finnell RH; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Kibar Z; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Marwan AI; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Melikishvili G; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Meltzer HS; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Mutchinick OM; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Stevenson DA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Mroczkowski HJ; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ostrander B; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Schindewolf E; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Moldenhauer J; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Zackai EH; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Emanuel BS; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Garcia-Minaur S; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Nowakowska BA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Stevenson RE; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
  • Zaki MS; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
Science ; 384(6695): 584-590, 2024 05 03.
Article em En | MEDLINE | ID: mdl-38696583
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromossomos Humanos Par 22 / Deleção Cromossômica / Meningomielocele Limite: Animals / Female / Humans / Male Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromossomos Humanos Par 22 / Deleção Cromossômica / Meningomielocele Limite: Animals / Female / Humans / Male Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article