PMID- 35846113
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220719
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 13
DP  - 2022
TI  - Novel CNNM2 Mutation Responsible for Autosomal-Dominant Hypomagnesemia With 
      Seizure.
PG  - 875013
LID - 10.3389/fgene.2022.875013 [doi]
LID - 875013
AB  - CNNM2 is primarily expressed in the brain and distal convoluted tubule (DCT) of 
      the kidney. Mutations in CNNM2 have been reported to cause hypomagnesemia, 
      seizure, and intellectual disability (HSMR) syndrome. However, the clinical and 
      functional effect of CNNM2 mutations remains incompletely understood. We report 
      our clinical encounter with a 1-year-old infant with HSMR features. Mutation 
      screening for this trio family was performed using next-generation sequencing 
      (NGS)-based whole exome sequencing (WES) with the identified mutation verified by 
      Sanger sequencing. We identified a de novo heterozygous mutation c.G1439T (R480L) 
      in the essential cystathionine beta-synthase (CBS) domain of CNNM2 encoding CNNM2 
      (cyclin M2) without any other gene mutations related to hypomagnesemia. The amino 
      acid involved in this missense mutation was conserved in different species. It 
      was also found to be pathogenic based on the different software prediction models 
      and ACGME criteria. In vitro studies revealed a higher expression of the 
      CNNM2-R480L mutant protein compared to that of the wild-type CNNM2. Like the 
      CNNM2-wild type, proper localization of CNNM2-R480L was shown on 
      immunocytochemistry images. The Mg(2+) efflux assay in murine DCT (mDCT) cells 
      revealed a significant increase in intracellular Mg(2+) green in CNNM2-R480L 
      compared to that in CNNM2-WT. By using a simulation model, we illustrate that the 
      R480L mutation impaired the interaction between CNNM2 and ATP-Mg(2+). We propose 
      that this novel R480L mutation in the CNNM2 gene led to impaired binding between 
      Mg(2+)-ATP and CNNM2 and diminished Mg(2+) efflux, manifesting clinically as 
      refractory hypomagnesemia.
CI  - Copyright (c) 2022 Tseng, Yang, Sung, Ding, Hsu, Chu and Lin.
FAU - Tseng, Min-Hua
AU  - Tseng MH
AD  - Division of Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital 
      and Chang Gung University, Taoyuan, Taiwan.
AD  - Department of Pediatrics, Xiamen Chang Gung Hospital, Ximen, China.
FAU - Yang, Sung-Sen
AU  - Yang SS
AD  - Division of Nephrology, Department of Internal Medicine, Tri-Service General 
      Hospital, National Defense Medical Center, Taipei, Taiwan.
FAU - Sung, Chih-Chien
AU  - Sung CC
AD  - Division of Nephrology, Department of Internal Medicine, Tri-Service General 
      Hospital, National Defense Medical Center, Taipei, Taiwan.
FAU - Ding, Jhao-Jhuang
AU  - Ding JJ
AD  - Department of Pediatrics, Tri-Service General Hospital, National Defense Medical 
      Center, Taipei, Taiwan.
FAU - Hsu, Yu-Juei
AU  - Hsu YJ
AD  - Division of Nephrology, Department of Internal Medicine, Tri-Service General 
      Hospital, National Defense Medical Center, Taipei, Taiwan.
FAU - Chu, Shih-Ming
AU  - Chu SM
AD  - Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital 
      and Chang Gung University, Taoyuan, Taiwan.
FAU - Lin, Shih-Hua
AU  - Lin SH
AD  - Division of Nephrology, Department of Internal Medicine, Tri-Service General 
      Hospital, National Defense Medical Center, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20220629
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC9277586
OTO - NOTNLM
OT  - CNNM2
OT  - HSMR syndrome
OT  - hypomagnesemia
OT  - renal magnesium wasting
OT  - seizure
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- 2022/07/19 06:00
MHDA- 2022/07/19 06:01
PMCR- 2022/06/29
CRDT- 2022/07/18 03:58
PHST- 2022/02/19 00:00 [received]
PHST- 2022/04/27 00:00 [accepted]
PHST- 2022/07/18 03:58 [entrez]
PHST- 2022/07/19 06:00 [pubmed]
PHST- 2022/07/19 06:01 [medline]
PHST- 2022/06/29 00:00 [pmc-release]
AID - 875013 [pii]
AID - 10.3389/fgene.2022.875013 [doi]
PST - epublish
SO  - Front Genet. 2022 Jun 29;13:875013. doi: 10.3389/fgene.2022.875013. eCollection 
      2022.