PMID- 36685872
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 13
DP  - 2022
TI  - Doubly bi-allelic variants of MTHFR and MTHFD1 in a Chinese patient with 
      hyperhomocysteinemia and failure of folic acid therapy.
PG  - 964990
LID - 10.3389/fgene.2022.964990 [doi]
LID - 964990
AB  - Background: Hyperhomocysteinemia (HHcy) is a risk factor for thromboembolic 
      disease. Defects in one-carbon metabolism (1-CM)-related genes, such as 
      methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate 
      dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1), 
      can cause HHcy and may also affect the efficacy of folic acid therapy. The 
      details of mechanisms are yet to be further investigated. Method: We described a 
      Chinese family with hereditary HHcy. The proband suffered from severe 
      thromboembolic disease and experienced failure of folic acid therapy. Two sons of 
      the proband were also diagnosed with HHcy but were sensitive to folic acid 
      therapy. Whole-exome sequencing (WES) was conducted to evaluate the genetic 
      lesion of this family. Results: Compound heterozygous variants (a common 
      polymorphism, p. A222V, and a novel variant, p. C631*fs*1) of the MTHFR gene and 
      a homozygous missense variant (p. K134R) of the MTHFD1 gene were identified in 
      the proband. The two sons, with successful intervention, only harbored the 
      homozygous p. A222V variant of the MTHFR gene. Conclusion: The clinical 
      manifestations and genetic research synergistically confirmed the diagnosis of 
      HHcy and clarified the failure of folic acid therapy in the proband caused by 
      doubly bi-allelic variants of the MTHFR and MTHFD1 genes. Our study increased our 
      understanding of the molecular basis of 1-CM-related gene defects on folic acid 
      therapy in HHcy.
CI  - Copyright (c) 2023 Liu, Ding, Sheng, Sun, Liu and Zhang.
FAU - Liu, Yu-Xing
AU  - Liu YX
AD  - Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.
AD  - Department of Cell Biology, School of Life Sciences, Central South University, 
      Changsha, China.
FAU - Ding, Man-Hua
AU  - Ding MH
AD  - Department of Radiotherapy, Xuzhou Cancer Hospital, Xuzhou, China.
FAU - Sheng, Yue
AU  - Sheng Y
AD  - Department of Cell Biology, School of Life Sciences, Central South University, 
      Changsha, China.
FAU - Sun, Meng-Fei
AU  - Sun MF
AD  - Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.
FAU - Liu, Lv
AU  - Liu L
AD  - Department of Respiratory Medicine, Diagnosis and Treatment Center of Respiratory 
      Disease, The Second Xiangya Hospital of Central South University, Changsha, 
      China.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20230104
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC9845700
OTO - NOTNLM
OT  - MTHFD1
OT  - MTHFR
OT  - folic acid
OT  - hyperhomocysteinemia
OT  - whole-exome sequencing
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/01/24 06:00
MHDA- 2023/01/24 06:01
PMCR- 2023/01/04
CRDT- 2023/01/23 04:42
PHST- 2022/07/11 00:00 [received]
PHST- 2022/11/30 00:00 [accepted]
PHST- 2023/01/23 04:42 [entrez]
PHST- 2023/01/24 06:00 [pubmed]
PHST- 2023/01/24 06:01 [medline]
PHST- 2023/01/04 00:00 [pmc-release]
AID - 964990 [pii]
AID - 10.3389/fgene.2022.964990 [doi]
PST - epublish
SO  - Front Genet. 2023 Jan 4;13:964990. doi: 10.3389/fgene.2022.964990. eCollection 
      2022.