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:C0238111 (
Lennox-Gastaut syndrome
)
861
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The childhood epileptic encephalopathies (EE's) are seizure disorders that broadly impact development including cognitive, sensory and motor progress with severe consequences and comorbidities. Recently, mutations in DNM1 (dynamin 1) have been implicated in two EE syndromes,
Lennox-Gastaut
Syndrome and Infantile Spasms. Dnm1 encodes dynamin 1, a large multimeric GTPase necessary for activity-dependent membrane recycling in neurons, including synaptic vesicle endocytosis. Dnm1Ftfl or "fitful" mice carry a spontaneous mutation in the mouse ortholog of DNM1 and recapitulate many of the disease features associated with human DNM1 patients, providing a relevant disease model of human EE's. In order to examine the cellular etiology of seizures and behavioral and neurological comorbidities, we engineered a conditional Dnm1Ftfl mouse model of DNM1 EE. Observations of Dnm1Ftfl/flox mice in combination with various neuronal subpopulation specific cre strains demonstrate unique seizure phenotypes and clear separation of major neurobehavioral comorbidities from severe seizures associated with the germline model. This demonstration of pleiotropy suggests that treating seizures per se may not prevent severe comorbidity observed in EE associated with
dynamin
-1 mutations, and is likely to have implications for other genetic forms of EE.
...
PMID:Independent Neuronal Origin of Seizures and Behavioral Comorbidities in an Animal Model of a Severe Childhood Genetic Epileptic Encephalopathy. 2612 63
Objective:
To analyze the clinical and gene mutation characteristics of
dynamin
-1 (DNM1)-related infantile spasms.
Method:
Clinical, laboratory and genetic data of one case of DNM1-related infantile spasms diagnosed by Xiangya Hospital in September 2015 were analyzed.Through taking "Dynamin-1" "DNM1" as key words to search at CNKI, Wanfang, PubMed and OMIM to date (April 2016), the clinical characteristics of 9 reported cases of DNM1-related epileptic encephalopathy in international literature with our case were reviewed.
Result:
The boy is the second child of healthy and nonconsanguineous parents.At 7 months, he started to have seizures with head dropping, and he was brought for the first time to our hospital at the age of 17 months.The patient presented with severe psychomotor retardation, epilepsy, muscular hypotonia, and electroencephalography showed hypsarhythmia.He received 28 days of adrenocorticotropic hormone (ACTH) therapy.After that, his seizures were improved with valproic acid and levetiracetam, and disappeared between 3 years and 5 months to 5 years and 5 months of age on treatment with valproic acid only.Exome-sequencing study (trios) identified novel heterozygous mutation c. 443A>G (p.Glu148Arg) in DNM1. Up to now, 9 cases of epileptic encephalopathy (infantile spasms or
Lennox-Gastaut syndrome
) associated with de novo DNM1 gene mutations have been reported.
Conclusion:
The main clinical features of DNM1 mutations include intractable seizures, intellectual disability, developmental delay, hypotonia, and developmental delay before the onset of seizures.
...
PMID:[Dynamin-1-related infantile spasms: a case report and review of literature]. 2780 96
