PMID- 33917565
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230920
IS  - 2075-1729 (Print)
IS  - 2075-1729 (Electronic)
IS  - 2075-1729 (Linking)
VI  - 11
IP  - 4
DP  - 2021 Apr 6
TI  - The Role of the Rare Variants in the Genes Encoding the Alpha-Ketoglutarate 
      Dehydrogenase in Alzheimer's Disease.
LID - 10.3390/life11040321 [doi]
LID - 321
AB  - There is increasing evidence that several mitochondrial abnormalities are present 
      in the brains of patients with Alzheimer's disease (AD). Decreased 
      alpha-ketoglutarate dehydrogenase complex (alphaKGDHc) activity was identified in 
      some patients with AD. The alphaKGDHc is a key enzyme in the Krebs cycle. This enzyme 
      is very sensitive to the harmful effect of reactive oxygen species, which gives 
      them a critical role in the Alzheimer and mitochondrial disease research area. 
      Previously, several genetic risk factors were described in association with AD. 
      Our aim was to analyze the associations of rare damaging variants in the genes 
      encoding alphaKGDHc subunits and AD. The three genes (OGDH, DLST, DLD) encoding 
      alphaKGDHc subunits were sequenced from different brain regions of 11 patients with 
      histologically confirmed AD and the blood of further 35 AD patients. As a control 
      group, we screened 134 persons with whole-exome sequencing. In all subunits, a 
      one-one rare variant was identified with unknown significance based on American 
      College of Medical Genetics and Genomics (ACMG) classification. Based on the 
      literature research and our experience, R263H mutation in the DLD gene seems 
      likely to be pathogenic. In the different cerebral areas, the alphaKGDHc mutational 
      profile was the same, indicating the presence of germline variants. We 
      hypothesize that the heterozygous missense R263H in the DLD gene may have a role 
      in AD as a mild genetic risk factor.
FAU - Csaban, Dora
AU  - Csaban D
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, H-1082 
      Budapest, Hungary.
FAU - Pentelenyi, Klara
AU  - Pentelenyi K
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, H-1082 
      Budapest, Hungary.
FAU - Toth-Bencsik, Renata
AU  - Toth-Bencsik R
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, H-1082 
      Budapest, Hungary.
FAU - Illes, Anett
AU  - Illes A
AD  - PentaCore Laboratory Budapest, H-1094 Budapest, Hungary.
FAU - Grosz, Zoltan
AU  - Grosz Z
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, H-1082 
      Budapest, Hungary.
FAU - Gezsi, Andras
AU  - Gezsi A
AD  - Department of Measurement and Information Systems, Budapest University of 
      Technology and Economics, H-1117 Budapest, Hungary.
FAU - Molnar, Maria Judit
AU  - Molnar MJ
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, H-1082 
      Budapest, Hungary.
LA  - eng
GR  - KTIA_13_NAP-A-III/6/Hungarian National Brain Research Program/
GR  - OTKA PD 134449/Hungarian Academy of Sciences and the National Research/
PT  - Journal Article
DEP - 20210406
PL  - Switzerland
TA  - Life (Basel)
JT  - Life (Basel, Switzerland)
JID - 101580444
PMC - PMC8067443
OTO - NOTNLM
OT  - Alzheimer
OT  - DLD
OT  - alpha-ketoglutarate dehydrogenase complex
OT  - brain tissue
OT  - dementia
OT  - rare variants
OT  - alphaKGDHc
COIS- The authors declare no conflict of interest.
EDAT- 2021/05/01 06:00
MHDA- 2021/05/01 06:01
PMCR- 2021/04/06
CRDT- 2021/04/30 01:06
PHST- 2021/03/23 00:00 [received]
PHST- 2021/04/02 00:00 [revised]
PHST- 2021/04/03 00:00 [accepted]
PHST- 2021/04/30 01:06 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/05/01 06:01 [medline]
PHST- 2021/04/06 00:00 [pmc-release]
AID - life11040321 [pii]
AID - life-11-00321 [pii]
AID - 10.3390/life11040321 [doi]
PST - epublish
SO  - Life (Basel). 2021 Apr 6;11(4):321. doi: 10.3390/life11040321.