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Identification of a missense ARSA mutation in metachromatic leukodystrophy and its potential pathogenic mechanism
Guo, Liyuan1,2; Jin, Bo3; Zhang, Yidan1,2; Wang, Jing1,2
First AuthorGuo, Liyuan
Correspondent Emailwangjing@psych.ac.cn
Contribution Rank1
Abstract

Background: Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal disorder caused by mutations inARSA. The biological processes of MLD disease caused by candidate pathogenic mutations in theARSAgene remain unclear. Methods: We used whole-exome sequencing (WES) and Sanger sequencing to identify the pathogenic mutation in a Chinese family. Literature review and protein three-dimensional structure prediction were performed to analyze the potential pathogenesis of the identified mutations. Overexpression cell models of wild-type and mutatedARSAgenes were constructed. The accumulated sulfatides and expression profiles in the cell models were detected, and a series of bioinformatics analyses were carried out to compare the biological changes caused by the candidate pathogenic mutations. Results: We identified anARSAc.925G>A homozygous mutation from a Chinese late-infantile MLD patient, the first report of this mutation in East Asia. The literature and protein structure analysis indicated that three types of mutations at c.925G (c.925G>A, c.925G>T, c.925G>C) were pathogenic. The overexpression of wild-type or mutatedARSAgenes influenced the accumulation of sulfatides. The co-expression modules in the mutated cell models were constructed by genes related to calcium signaling and vesicle transport. Conclusion: Our results identified a pathogenic mutation,ARSAhomozygosity c.925G>A, from a Chinese MLD family. The pathogenic mechanism of theARSAmutation in MLD was identified, which may suggest new approaches to diagnosis and treatment.

KeywordARSA gene mutation bioinformatics analysis expression profiling Metachromatic leukodystrophy mutation effect prediction
2020-09-01
Language英语
DOI10.1002/mgg3.1478
Source PublicationMOLECULAR GENETICS & GENOMIC MEDICINE
ISSN2324-9269
Pages11
Subtypearticle
Indexed BySCI
Funding ProjectCAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences
PublisherWILEY
WOS KeywordPSAP GENES ; ARYLSULFATASE ; UPDATE
WOS Research AreaGenetics & Heredity
WOS SubjectGenetics & Heredity
WOS IDWOS:000564544200001
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/32634
Collection中国科学院心理健康重点实验室
Corresponding AuthorWang, Jing
Affiliation1.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, 16 Lincui Rd, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
3.Nanjing Med Univ, Childrens Hosp, Dept Neurol, Nanjing, Jiangsu, Peoples R China
First Author AffilicationKey Laboratory of Mental Health, CAS
Corresponding Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Guo, Liyuan,Jin, Bo,Zhang, Yidan,et al. Identification of a missense ARSA mutation in metachromatic leukodystrophy and its potential pathogenic mechanism[J]. MOLECULAR GENETICS & GENOMIC MEDICINE,2020:11.
APA Guo, Liyuan,Jin, Bo,Zhang, Yidan,&Wang, Jing.(2020).Identification of a missense ARSA mutation in metachromatic leukodystrophy and its potential pathogenic mechanism.MOLECULAR GENETICS & GENOMIC MEDICINE,11.
MLA Guo, Liyuan,et al."Identification of a missense ARSA mutation in metachromatic leukodystrophy and its potential pathogenic mechanism".MOLECULAR GENETICS & GENOMIC MEDICINE (2020):11.
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