A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism

doi:10.1016/j.cca.2021.12.023

科研成果详情

题名	A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism
作者	Ying, Yingfen1; Ye, Jinbin 1; Chen, Yamin2; Chen, Qishu1; Chen, Yilu1; Lu, Xiaosheng1; Xi, Haitao 1; Gu, Feng2; Pan, Deng2; Zhao, Junzhao1
发表日期	2022-02-01
发表期刊	Clinica chimica acta; international journal of clinical chemistry 影响因子和分区
语种	英语
原始文献类型	Article
关键词	CRISSPR/Cas9 ELANE gene mutation Exome sequencing Molecular diagnosis Paternal germline mosaicism Severe congenital neutropenia.
其他关键词	SOMATIC MOSAICISM ; BREAK REPAIR ; CRISPR/CAS9 ; SELECTION ; ELASTASE ; CELLS ; STEM ; AGE
摘要	Background:Clinical and genetic characteristics of ELANE mutation of a 3-year-old male who had a severe congenital neutropenia (SCN) were examined. We then investigated whether CRISPR/Cas9-mediated gene editing could correct the mutation. Procedure:The proband underwent extensive clinical assessments, such as exome sequencing and bioinformatics analysis, so that pathogenic genes could be identified. Sanger sequencing was also utilized for confirmation. The cell line, 293-ELANE, harboring ELANE mutation was generated, and the mutation was then corrected by CRISPR/Cas9-mediated homology-directed repair (HDR). Results:The ELANE gene test in the proband unveiled a heterozygous de novo missense mutation: c. 248T > A (p.V83D), which was not detected in his asymptomatic parents who had provided peripheral blood samples. We found that 46.01% of his father's sperm cells had the same mutation. These results demonstrate that the proband inherited the ELANE mutation from his father, who had an average neutrophil count but had a germline mosaicism. The highest repair efficiency of CRISPR/Cas9-mediated HDR for 293-ELANE is 4.43%. Conclusions:We identified a missense mutation (p.V83D) in ELANE that causes SCN. This is the first report on paternal semen mosaicism of an ELANE mutation. Our study paves the way for preimplantation genetic diagnosis (PGD) based on ELANE mutation prevention and clinical treatment of congenital disabilities.
资助项目	Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University[PRR9990626];
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	0009-8981
EISSN	1873-3492
卷号	526 页码:14-20.
DOI	10.1016/j.cca.2021.12.023
页数	7
WOS类目	Medical Laboratory Technology
WOS研究方向	Medical Laboratory Technology
WOS记录号	WOS:000799165800003
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	34968504
SCOPUSEID	2-s2.0-85121931506
通讯作者地址	[Pan, Deng]School of Ophthalmology and Optometry,Eye Hospital,Wenzhou Medical University,State Key Laboratory and Key Laboratory of Vision Science,Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry,Wenzhou,325027,China
Scopus学科分类	Biochemistry;Clinical Biochemistry;Biochemistry (medical)
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/33275
专题	第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Pan, Deng
作者单位	1.Reproductive Center,Department of Obstetrics and Gynecology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,325027,China; 2.School of Ophthalmology and Optometry,Eye Hospital,Wenzhou Medical University,State Key Laboratory and Key Laboratory of Vision Science,Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry,Wenzhou,325027,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Ying, Yingfen,Ye, Jinbin,Chen, Yamin,et al. A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism[J]. Clinica chimica acta; international journal of clinical chemistry,2022,526:14-20..
APA	Ying, Yingfen., Ye, Jinbin., Chen, Yamin., Chen, Qishu., Chen, Yilu., ... & Zhao, Junzhao. (2022). A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism. Clinica chimica acta; international journal of clinical chemistry, 526, 14-20..
MLA	Ying, Yingfen,et al."A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism".Clinica chimica acta; international journal of clinical chemistry 526(2022):14-20..