二分脊椎の発生に関する新たな洞察(New Insight Into Genesis of Spina Bifida)

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2024-05-08 カリフォルニア大学サンディエゴ校(UCSD)

二分脊椎の発生に関する新たな洞察(New Insight Into Genesis of Spina Bifida)The causes of spina bifida, in which the spinal cord doesn’t develop properly, are unknown. A newly released study demonstrates a link between a chromosomal deletion and the risk of a baby being born with spina bifida. Photo credit: Jevtic/iStock

カリフォルニア大学サンディエゴ校の研究グループが、脊椎二分症(spina bifida)の原因として、一般的な染色体微小欠失との関連を初めて明らかにしました。この欠失は2,500人に1人の割合で発生し、脊椎二分症のリスクを一般より10倍以上高めることが判明しました。また、この研究は葉酸がCRKL遺伝子の介在する脊椎二分症の発症リスクや重症度を低減する可能性があることを示唆しています。これらの発見は、将来の治療法開発に貢献すると期待されています。この研究結果は「Science」誌に掲載されました。

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一般的な22q11.2欠失が介在する髄膜瘤のリスク Risk of meningomyelocele mediated by the common 22q11.2 deletion

KENG IOI VONG, SANGMOON LEE, KIT SING AU, T. BLAINE CROWLEY, […], AND JOSEPH G. GLEESON
Science  Published:2 May 2024
DOI:https://doi.org/10.1126/science.adl1624

Editor’s summary

Meningomyelocele is a severe type of spina bifida, and it is also the most common type. Although its incidence has decreased in recent decades after many countries introduced folate supplementation into staple foods, meningomyelocele remains a challenge in many parts of the world. Moreover, dietary fortification with folate is not always effective, and some medications and medical conditions can also affect disease risk, as can genetic predisposition. To study meningomyelocele genetics, Vong et al. established the large, multinational Spina Bifida Sequencing Consortium. Based on data from this consortium, the authors identified chromosomal 22q11.2 deletions that greatly increase the risk of meningomyelocele and then showed how the loss of a specific gene on this chromosome can alter neural tube development. —Yevgeniya Nusinovich

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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