Identification and functional analysis of a novel phospholipase D2 gene mutation associated with familial systemic lupus erythematosus.
10.11817/j.issn.1672-7347.2021.190589
- Author:
Lin PENG
1
;
Xinke YUAN
2
;
Lixiao CHEN
2
;
Sijia CHEN
2
;
Ke CHEN
3
Author Information
1. Department of Nephrology, First Hospital of Changsha, Changsha 410005. plin1018@163.com.
2. Department of Nephrology, First Hospital of Changsha, Changsha 410005.
3. Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China. chenke520@yeah.net.
- Publication Type:Journal Article
- Keywords:
HRAS;
high-throughput genome-wide sequencing;
phospholipase D2 gene;
phospholipase D2-Ras signaling pathway;
systemic lupus erythematosus
- MeSH:
Case-Control Studies;
Female;
High-Throughput Nucleotide Sequencing;
Humans;
Lupus Erythematosus, Systemic/genetics*;
Lupus Nephritis;
Mutation;
Phospholipase D
- From:
Journal of Central South University(Medical Sciences)
2021;46(3):234-239
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Systemic lupus erythematosus (SLE) is a kind of autoimmune inflammatory connective tissue disease which seriously endangers human health. Genetic factors play a key role in the pathogenesis of SLE. This study aims to investigate a novel phospholipase D2 (PLD2) mutation associated with familial SLE, and further explore the underlying mechanism of the mutation in SLE.
METHODS:The blood samples from a SLE patient, the patient's parents, and 147 normal controls were collected and DNA was extracted. Whole genome high-throughput sequencing was performed in the patient and her parents and the results were further analyzed by various bioinformatics methods. The wild type (wt), mutant type (mu), and negative control PLD2 plasmids were further constructed and transfected into 293 cells. The expression level of HRAS protein in 293 cells was detected by Western blotting.
RESULTS:In this SLE family, the female SLE patient and her mother, 1 in generation II and 1 in generation III had typical clinical manifestations of SLE, and all of them had lupus nephritis at early stage. The genetic characteristics are consistent with autosomal dominant inheritance. A novel PLD2 heterozygous mutation (c.2722C>T) was found in the patient and her mother, but not in her father and other normal controls. Compared with wtPLD2 plasmid and negative control PLD2 plasmid, the expression of HRAS in 293 cells transfected with muPLD2 plasmid was significantly up-regulated (both
CONCLUSIONS:PLD2 c.2722C>T mutation may be one of the pathogeny of SLE in this family.
