Generation of an induced pluripotent stem cell line from a patient with global development delay carrying DYRK1A mutation (c.1730T>A) and a gene correction isogenic iPSC line

Ling Ma; Ziyan Wu; Qingyuan Tang; Xiaoli Ji; Yuting Mei; Ting Peng; Qiong Xu; Wenhao Zhou; Man Xiong

doi:10.1016/j.scr.2021.102305

Generation of an induced pluripotent stem cell line from a patient with global development delay carrying DYRK1A mutation (c.1730T>A) and a gene correction isogenic iPSC line

Stem Cell Res. 2021 May:53:102305. doi: 10.1016/j.scr.2021.102305. Epub 2021 Mar 20.

Authors

Ling Ma¹, Ziyan Wu², Qingyuan Tang³, Xiaoli Ji⁴, Yuting Mei⁴, Ting Peng⁴, Qiong Xu⁵, Wenhao Zhou⁶, Man Xiong⁷

Affiliations

¹ Stem Cell Research Center, Institute of Pediatrics, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China; Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
² Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
³ Stem Cell Research Center, Institute of Pediatrics, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
⁴ Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
⁵ Department of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, China. Electronic address: xuqiong@fudan.edu.cn.
⁶ Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China; Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China. Electronic address: zwhchfu@126.com.
⁷ Stem Cell Research Center, Institute of Pediatrics, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China. Electronic address: man_xiong@hotmail.com.

PMID: 33813175
DOI: 10.1016/j.scr.2021.102305

Abstract

Mental retardation autosomal dominant 7 (MRD7), or DYRK1A Related Intellectual Disability Syndrome (OMIM 614104) is a developmental syndrome with microcephaly, intellectual disability, language delay and epileptic seizures. Haploinsufficiency of DYRK1A is the cause of MRD7. Here, we generated an induced pluripotent stem cell (iPSC) line with the mutation (DYRK1Ac.1730T>A) from the Peripheral blood mononuclear cell (PBMC) of a MRD7 patient along with an isogenic gene-corrected control iPSC line by CRISPR/Cas9 genome editing. Both iPSC lines showed full pluripotency, normal karyotype and differentiation capacity without integrating vectors. These DYRK1A mutant and isogenic gene-corrected iPSC control line provides a useful model to study the underlying molecular mechanisms of MRD7.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Clustered Regularly Interspaced Short Palindromic Repeats
Gene Editing
Humans
Induced Pluripotent Stem Cells*
Leukocytes, Mononuclear
Mutation