Sökning: id:"swepub:oai:prod.swepub.kib.ki.se:151437180" >
A Missense Variant ...
A Missense Variant in PDK1 Associated with Severe Neurodevelopmental Delay and Epilepsy
-
- Vaz, R (författare)
- Karolinska Institutet
-
- Wincent, J (författare)
- Karolinska Institutet
-
Elfissi, N (författare)
-
visa fler...
-
Forsblad, KR (författare)
-
- Pettersson, M (författare)
- Karolinska Institutet
-
Naess, K (författare)
-
- Wedell, A (författare)
- Karolinska Institutet
-
- Wredenberg, A (författare)
- Karolinska Institutet
-
- Lindstrand, A (författare)
- Karolinska Institutet
-
- Ygberg, S (författare)
- Karolinska Institutet
-
visa färre...
-
(creator_code:org_t)
- 2022-12-07
- 2022
- Engelska.
-
Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:12
- Relaterad länk:
-
http://kipublication...
-
visa fler...
-
https://doi.org/10.3...
-
visa färre...
Abstract
Ämnesord
Stäng
- The pyruvate dehydrogenase complex (PDC) is responsible for the conversion of pyruvate into acetyl-CoA, which is used for energy conversion in cells. PDC activity is regulated by phosphorylation via kinases and phosphatases (PDK/PDP). Variants in all subunits of the PDC and in PDK3 have been reported, with varying phenotypes including lactic acidosis, neurodevelopmental delay, peripheral neuropathy, or seizures. Here, we report a de novo heterozygous missense variant in PDK1 (c.1139G > A; p.G380D) in a girl with developmental delay and early onset severe epilepsy. To investigate the role of PDK1G380D in energy metabolism and neuronal development, we used a zebrafish model. In zebrafish embryos we show a reduced number of cells with mitochondria with membrane potential, reduced movements, and a delay in neuronal development. Furthermore, we observe a reduction in the phosphorylation of PDH-E1α by PDKG380D, which suggests a disruption in the regulation of PDC activity. Finally, in patient fibroblasts, a mild reduction in the ratio of phosphorylated PDH over total PDH-E1α was detected. In summary, our findings support the notion that this aberrant PDK1 activity is the cause of clinical symptoms in the patient.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Vaz, R
-
Wincent, J
-
Elfissi, N
-
Forsblad, KR
-
Pettersson, M
-
Naess, K
-
visa fler...
-
Wedell, A
-
Wredenberg, A
-
Lindstrand, A
-
Ygberg, S
-
visa färre...
- Artiklar i publikationen
-
Biomedicines
- Av lärosätet
-
Karolinska Institutet