Although genetic factors are considered a main etiology of epilepsy, the causes of genetic epilepsy in the majority of epilepsy patients remain unknown. Kinesin family member 1A (KIF1A), a neuron-specific motor protein that moves along with microtubules, is responsible for the transport of membranous organelles and synaptic vesicles. Variants of KIF1A have recently been associated with hereditary spastic paraplegia (HSP), hereditary sensory and autonomic neuropathy type 2 (HSANII), and intellectual disability. However, mutations in KIF1A have not been detected in patients with epilepsy. In our study, we conducted customized sequencing of epilepsy-related genes of a family with six patients with generalized epilepsy over three generations and identified a rare heterozygous mutation (c.1190C > A, p. Ala397Asp) in KIF1A. Whole-cell recordings from primary cultured neurons revealed that the mutant KIF1A increases the excitatory synaptic transmission but not the intrinsic excitability of neurons, and phenotype testing in zebrafish showed that this rare mutation results in epileptic seizure-like activity. These results provide new evidence demonstrating that KIF1A dysfunction is involved in epileptogenesis.
Epilepsy is one of the most common chronic neurological diseases in the world, with a high incidence, a high risk of sudden unexplained death, and diagnostic challenges. Exosomes are nanosized extracellular vesicles that are released into physical environments and carry a variety of biological information. Moreover, exosomes can also be synthesized and released from brain cells, passing through the blood-brain barrier, and can be detected in peripheral blood or cerebrospinal fluid. Our study using the tandem mass tag (TMT) approach showed that a total of 76 proteins were differentially expressed in serum exosomes between epilepsy patients and healthy controls, with 6 proteins increasing and 70 proteins decreasing. Analysis of large clinical samples and two mouse models of chronic epilepsy indicated that two significantly differentially expressed serum exosomal proteins, coagulation factor IX (F9) and thrombospondin-1 (TSP-1), represent promising biomarkers for the diagnosis of epilepsy, with area under the curve (AUC) values of up to 0.7776 (95% CI, 0.7306-0.8246) and 0.8534 (95% CI, 0.8152-0.8916), respectively. This is the first study of exosomal proteins in epilepsy, and it suggests that exosomes are promising new tools for the diagnosis of epilepsy.
Aim: To clarify the diagnostic value of the circulating free fatty acid (FFA) level for acute myocardial infarction (AMI) in coronary heart disease patients. Methods & results: A total of 1776 patients were screened by coronary angiography from October 2014 to February 2016. The plasma FFA level was significantly higher in coronary heart disease patients with lesions in three or more vessels than those with lesions in one or two vessels. Moreover, an elevated FFA level was identified as an independent risk factor for AMI on multivariate regression analysis and shown to be a sensitive and specific indicator for AMI diagnosis by receiver operating characteristic curve analysis. Conclusion: An elevated FFA level is an independent risk factor and independent diagnostic marker for AMI.
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