Dissection of contiguous gene effects for deletions around ERF on chromosome 19
Dissection of contiguous gene effects for deletions around ERF on chromosome 19
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DOI：
10.1002/humu.24213
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发表时间：
2021-05-16
期刊：
影响因子：
3.9
通讯作者：
Wilkie, Andrew O. M.
中科院分区：
文献类型：
--
作者：
Calpena, Eduardo;McGowan, Simon J.;Wilkie, Andrew O. M.
ERF的杂合基因内功能丧失突变，编码ETS转录因子，以前报道引起一种新的颅缝早闭综合征，表明ERF是单倍不足。我们描述了六个家庭窝藏杂合缺失，包括或接近，ERF，其中四个特点是全基因组测序和两个染色体微阵列。根据相关智力残疾（ID）的严重程度，我们确定了三种ERF相关缺失。最小的（32 kb）和唯一的遗传缺失包括两个额外的着丝粒基因，与ID无关。（264-314 kb），包括至少五个其他着丝粒基因与中度ID相关，表明这五个基因中的一个或多个的缺失导致ID。一个已知的身份基因发现ERF缺失的儿童应进行颅面评估，以排除隐性颅内压升高。
Heterozygous intragenic loss-of-function mutations of ERF, encoding an ETS transcription factor, were previously reported to cause a novel craniosynostosis syndrome, suggesting that ERF is haploinsufficient. We describe six families harboring heterozygous deletions including, or near to, ERF, of which four were characterized by whole-genome sequencing and two by chromosomal microarray. Based on the severity of associated intellectual disability (ID), we identify three categories of ERF-associated deletions. The smallest (32 kb) and only inherited deletion included two additional centromeric genes and was not associated with ID. Three larger deletions (264-314 kb) that included at least five further centromeric genes were associated with moderate ID, suggesting that deletion of one or more of these five genes causes ID. The individual with the most severe ID had a more telomerically extending deletion, including CIC, a known ID gene. Children found to harbor ERF deletions should be referred for craniofacial assessment, to exclude occult raised intracranial pressure.