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DOI 10.1126/science.adl1624

Медицинская библиотека · Science (New York, N.Y.) · 2024

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, Northrup Hope, McNamara Hanna K, Aldinger Kimberly A, Phelps Ian G, Deng Mei, Glass Ian A, Spina Bifida Sequencing Consortium‡, Morrow Bernice, McDonald-McGinn Donna M, Sanna-Cherchi Simone, Lamb Dolores J, Gleeson Joseph G

СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаПеревод в очереди

Аннотация

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.

Для цитирования: 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, Northrup Hope, McNamara Hanna K, Aldinger Kimberly A, Phelps Ian G, Deng Mei, Glass Ian A, Spina Bifida Sequencing Consortium‡, Morrow Bernice, McDonald-McGinn Donna M, Sanna-Cherchi Simone, Lamb Dolores J, Gleeson Joseph G. Risk of meningomyelocele mediated by the common 22q11.2 deletion.. Science (New York, N.Y.). 2024. DOI: 10.1126/science.adl1624.

Предметные рубрики MeSH

AnimalsFemaleHumansMaleMiceChromosome DeletionChromosomes, Human, Pair 22DiGeorge SyndromeExome SequencingFolic AcidFolic Acid DeficiencyMeningomyelocelePenetranceSpinal DysraphismRiskAdaptor Proteins, Signal Transducing
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