Novel Loss of Function Variant in BCKDK Causes a Treatable Developmental and Epileptic Encephalopathy.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
/ genetics
Amino Acid Sequence
Amino Acids, Branched-Chain
/ genetics
Autism Spectrum Disorder
/ genetics
Brain
/ pathology
Brain Diseases
/ genetics
Cell Line
Epilepsy, Generalized
/ genetics
Female
HEK293 Cells
Humans
Loss of Function Mutation
/ genetics
Male
Phosphorylation
/ genetics
Retrospective Studies
BCKDK deficiency
autism
branched-chain amino acids
epilepsy
newborn screening
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Feb 2022
18 Feb 2022
Historique:
received:
17
01
2022
revised:
10
02
2022
accepted:
16
02
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
29
3
2022
Statut:
epublish
Résumé
Branched-chain amino acids (BCAA) are essential amino acids playing crucial roles in protein synthesis and brain neurotransmission. Branched-chain ketoacid dehydrogenase (BCKDH), the flux-generating step of BCAA catabolism, is tightly regulated by reversible phosphorylation of its E1α-subunit. BCKDK is the kinase responsible for the phosphorylation-mediated inactivation of BCKDH. In three siblings with severe developmental delays, microcephaly, autism spectrum disorder and epileptic encephalopathy, we identified a new homozygous in-frame deletion (c.999_1001delCAC; p.Thr334del) of
Identifiants
pubmed: 35216372
pii: ijms23042253
doi: 10.3390/ijms23042253
pmc: PMC8878489
pii:
doi:
Substances chimiques
Amino Acids, Branched-Chain
0
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
EC 1.2.4.4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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