Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0036572 (
seizures
)
80,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Calcium/calmodulin-dependent protein kinase II (
CAMK2
) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay,
seizures
and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in
CAMK2A
. The missense mutation, p.His477Tyr is located in the CAMK2A association domain that is critical for its function and localization. Biochemically, the p.His477Tyr mutant is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme.
In vivo
, CAMK2A
H477Y
failed to rescue neuronal defects in
C. elegans
lacking
unc-43
, the ortholog of human
CAMK2A. In vitro
, neurons derived from patient iPSCs displayed profound synaptic defects. Together, our data demonstrate that a recessive germline mutation in
CAMK2A
leads to neurodevelopmental defects in humans and suggest that dysfunctional
CAMK2
paralogs may contribute to other neurological disorders.
...
PMID:A homozygous loss-of-function
CAMK2A
mutation causes growth delay, frequent seizures and severe intellectual disability. 2978 83
