Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.
Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.
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DOI：
10.1002/ajmg.a.62919
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发表时间：
2022-10
影响因子：
2
通讯作者：
Scott, Daryl A.
中科院分区：
文献类型：
--
作者：
Hardcastle, Amy;Berry, Aliska M.;Campbell, Ian M.;Zhao, Xiaonan;Liu, Pengfei;Gerard, Amanda E.;Rosenfeld, Jill A.;Sisoudiya, Saumya D.;Hernandez-Garcia, Andres;Loddo, Sara;Di Tommaso, Silvia;Novelli, Antonio;Dentici, Maria L.;Capolino, Rossella;Digilio, Maria C.;Graziani, Ludovico;Rustad, Cecilie F.;Neas, Katherine;Ferrero, Giovanni B.;Brusco, Alfredo;Di Gregorio, Eleonora;Wellesley, Diana;Beneteau, Claire;Joubert, Madeleine;Van den Bogaert, Kris;Boogaerts, Anneleen;McMullan, Dominic J.;Dean, John;Giuffrida, Maria G.;Bernardini, Laura;Varghese, Vinod;Shannon, Nora L.;Harrison, Rachel E.;Lam, Wayne W. K.;McKee, Shane;Turnpenny, Peter D.;Cole, Trevor;Morton, Jenny;Eason, Jacqueline;Jones, Marilyn C.;Hall, Rebecca;Wright, Michael;Horridge, Karen;Shaw, Chad A.;Chung, Wendy K.;Scott, Daryl A.
先天性腹股沟疝（CDH）可以单独发生，也可以与其他出生缺陷（CDH+）一起发生。分子病因只能在CDH病例的一个子集中确定。这在一定程度上是由于对隔膜发育基因的不完全理解。在这里，我们使用了DECIPHER数据库中收录的36名CDH+患者的临床和分子数据，以确定可能在膈肌发育中发挥作用的基因，并发现新的表型扩增。在这一组中，我们确定了携带有害序列或拷贝数变异的个体，这些变异影响CREBBP、SMARCA 4、UBA 2和USP 9 X。这些基因在隔膜发育中的作用得到了它们在发育中的小鼠隔膜中的表达、它们与已知CDH基因的相似性（使用来自先前发表和验证的机器学习算法的数据）和/或CDH在其他具有相关遗传疾病的个体中的存在的支持。我们的研究结果证明了DECIPHER和其他公共数据库的数据如何用于识别新的表型扩增，并表明CREBBP，SMARCA 4，UBA 2和USP 9 X在隔膜发育中发挥作用。
Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are catalogued in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development.
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影响因子：
9.8
作者：
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通讯作者：
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DOI：
10.1002/path.4926
发表时间：
2017-09
期刊：
The Journal of pathology
影响因子：
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作者：
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通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
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