PMID- 38075676
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231211
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 14
DP  - 2023
TI  - Expanding the phenotype and metabolic basis of ATP6AP2-congenital disorder of 
      glycosylation in a Chinese patient with a novel variant c.185G>A (p.Gly62Glu).
PG  - 1264237
LID - 10.3389/fgene.2023.1264237 [doi]
LID - 1264237
AB  - Background: A rare X-linked hereditary condition known as ATP6AP2-congenital 
      disorder of glycosylation (ATP6AP2-CDG) is caused by pathogenic variants in 
      ATP6AP2, resulting in autophagic misregulation with reduced siganling of 
      mammalian target of rapamycin (mTOR) that clinically presents with aberrant 
      protein glycosylation, hepatosteatosis, immunodeficiency, cutis laxa, and 
      psychomotor dysfunction. To date, only two missense mutations have been reported 
      in three patients from two unrelated families. Methods: In order to extend the 
      profiles of phenotype and genotype associated with ATP6AP2-CDG, we assessed the 
      clinical history, whole exome sequencing (WES), and liver histology as well as 
      immunohistochemistry in a Chinese patient, and performed quantitative real-time 
      polymerase chain reaction (qRT-PCR), Western blotting and untargeted metabolomics 
      in genetic exogenously constructed cells. Results: The 11-month-old Chinese boy 
      presented with recurrent jaundice, cutis laxa, cirrhosis, growth retardation, 
      coagulopathy, anemia, and cardiomegaly, and underwent liver transplantation. A 
      novel mutation, c.185G>A (p.Gly62Glu), was identified in exon 3 of ATP6AP2. The 
      expression of ATP6AP2 was observed to remain unchanged in the liver sample of the 
      patient as well as in HEK293T cells harboring the p.Gly62Glu. This missense 
      mutation was found to dysregulate autophagy and mTOR signaling. Moreover, 
      metabolomics analysis revealed that the exogenously introduced Gly62Glu mutant 
      resulted in the downregulation of numerous metabolites involved in lipid 
      metabolism pathway. Conclusion: This study may enable a more detailed exploration 
      of its precise pathogenesis and potential therapeutic interventions.
CI  - Copyright (c) 2023 Fang, Wang, Chen and Xie.
FAU - Fang, Yuan
AU  - Fang Y
AD  - Department of Pathology, Anhui Provincial Children's Hospital, Hefei, China.
FAU - Wang, Yi-Zhen
AU  - Wang YZ
AD  - Department of Pathology, Anhui Provincial Children's Hospital, Hefei, China.
FAU - Chen, Lian
AU  - Chen L
AD  - Department of Pathology, Children's Hospital of Fudan University, Shanghai, 
      China.
FAU - Xie, Xin-Bao
AU  - Xie XB
AD  - Department of Hepatology, Children's Hospital of Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20231122
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC10702736
OTO - NOTNLM
OT  - ATP6AP2
OT  - X-linked
OT  - cirrhosis
OT  - congenital disorders of glycosylation
OT  - hereditary
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- 2023/12/11 06:45
MHDA- 2023/12/11 06:46
PMCR- 2023/11/22
CRDT- 2023/12/11 06:01
PHST- 2023/08/04 00:00 [received]
PHST- 2023/10/31 00:00 [accepted]
PHST- 2023/12/11 06:46 [medline]
PHST- 2023/12/11 06:45 [pubmed]
PHST- 2023/12/11 06:01 [entrez]
PHST- 2023/11/22 00:00 [pmc-release]
AID - 1264237 [pii]
AID - 10.3389/fgene.2023.1264237 [doi]
PST - epublish
SO  - Front Genet. 2023 Nov 22;14:1264237. doi: 10.3389/fgene.2023.1264237. eCollection 
      2023.