PMID- 34815077
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220210
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 591
DP  - 2022 Feb 5
TI  - Two novel STAT1 mutations cause Mendelian susceptibility to mycobacterial 
      disease.
PG  - 124-129
LID - S0006-291X(21)01547-3 [pii]
LID - 10.1016/j.bbrc.2021.11.036 [doi]
AB  - Mendelian susceptibility to mycobacterial disease (MSMD) is a rare monogenetic 
      disease, which is characterized by susceptibility to some weakly virulent 
      mycobacteria. Here, we explored the pathogenic genes and molecular mechanisms of 
      MSMD patients. We recruited three patients diagnosed with MSMD from two families. 
      Two novel mutations (c.1228A > G, p.K410E and c.2071A > G, p.M691V) in STAT1 gene 
      were identified from two families. The translocation of K410E mutant STAT1 
      protein into nucleus was not affected. The binding ability between 
      gamma-activating sequence (GAS) and K410E mutant STAT1 protein was significantly 
      reduced, which will reduce the interaction between STAT1 protein with the 
      promoters of target genes. The M691V mutant STAT1 protein cannot translocate into 
      the nucleus after IFN-gamma stimulation, which will affect the STAT1 protein form 
      gamma-activating factors (GAF) and bind the GAS in the promoter region of 
      downstream target genes. Taken together, our results showed that the mutation of 
      K410E led to impaired binding of STAT1 to target DNA, and the mutation of M691V 
      prevented the transport of STAT1 into the nucleus, which led to MSMD. Together, 
      we identified two novel mutations (c.1228A > G, p.K410E and c.2071A > G, p.M691V) 
      in STAT1 gene in MSMD patients, and deciphered the molecular mechanism of MSMD 
      caused by STAT1 mutations.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Liu, Zhenxing
AU  - Liu Z
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Zhou, Mi
AU  - Zhou M
AD  - Wuhan Jinyintan Hospital, Wuhan, Hubei, China.
FAU - Yuan, Chao
AU  - Yuan C
AD  - Zhaoqing Medical College, Zhaoqing, Guangdong, China.
FAU - Ni, Zhengyi
AU  - Ni Z
AD  - Wuhan Jinyintan Hospital, Wuhan, Hubei, China.
FAU - Liu, Wenqiang
AU  - Liu W
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Tan, Yang
AU  - Tan Y
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Zhang, Dazhi
AU  - Zhang D
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Zhou, Xiaopei
AU  - Zhou X
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Zou, Tingting
AU  - Zou T
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Wang, Jiarui
AU  - Wang J
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Hou, Meiqi
AU  - Hou M
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Peng, Xuejie
AU  - Peng X
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China.
FAU - Zhang, Xianqin
AU  - Zhang X
AD  - Key Laboratory of Molecular Biophysics of the Ministry of Education, College of 
      Life Science and Technology and Center for Human Genome Research, Huazhong 
      University of Science and Technology, Wuhan, Hubei, 430074, China. Electronic 
      address: xqzhang04@hust.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211114
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Mutant Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cell Nucleus/metabolism
MH  - DNA/metabolism
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Male
MH  - Mutant Proteins/chemistry/genetics
MH  - Mutation/*genetics
MH  - Mycobacterium Infections/*genetics/*microbiology
MH  - Pedigree
MH  - Protein Binding
MH  - Protein Domains
MH  - Protein Transport
MH  - STAT1 Transcription Factor/chemistry/*genetics/metabolism
MH  - Subcellular Fractions/metabolism
OTO - NOTNLM
OT  - Bacillus Calmette-Guerin
OT  - IFN-gamma
OT  - Mendelian susceptibility to mycobacterial disease
OT  - Mycobacteria
OT  - STAT1 mutation
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2021/11/25 06:00
MHDA- 2022/02/11 06:00
CRDT- 2021/11/24 05:41
PHST- 2021/09/30 00:00 [received]
PHST- 2021/11/10 00:00 [accepted]
PHST- 2021/11/25 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/11/24 05:41 [entrez]
AID - S0006-291X(21)01547-3 [pii]
AID - 10.1016/j.bbrc.2021.11.036 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2022 Feb 5;591:124-129. doi: 
      10.1016/j.bbrc.2021.11.036. Epub 2021 Nov 14.