Abstract
Tuberous sclerosis complex (TSC) is a genetic disease characterized by seizures, mental deficiency, and abnormalities of the skin, brain, kidney, heart, and lungs. TSC is inherited in an autosomal dominant manner and is caused by variations in either the TSC1 or TSC2 gene. TSC-related epilepsy (TRE) is the most prevalent and challenging clinical feature of TSC, and more than half of the patients have refractory epilepsy. In clinical practice, we found several patients of intractable epilepsy caused by TSC1 truncating mutations. To study the changes of protein expression in the brain, three cases of diseased brain tissue with TSC1 truncating mutation resected in intractable epilepsy operations and three cases of control brain tissue resected in craniocerebral trauma operations were collected to perform protein spectrum detection, and then the data-independent acquisition (DIA) workflow was used to analyze differentially expressed proteins. As a result, there were 55 up- and 55 down-regulated proteins found in the damaged brain tissue with TSC1 mutation compared to the control. Further bioinformatics analysis revealed that the differentially expressed proteins were mainly concentrated in the synaptic membrane between the patients with TSC and the control. Additionally, TSC1 truncating mutations may affect the pathway of amino acid metabolism. Our study provides a new idea to explore the brain damage mechanism caused by TSC1 mutations.
Highlights
Epilepsy is one of the most common neurological diseases in the clinic
We found several patients of intractable epilepsy caused by TSC1 truncating mutations
We reported clinical features, mutation analyses and brain proteomic profiling of three surgical cases of intractable epilepsy caused by truncating mutations in TSC1
Summary
Epilepsy is one of the most common neurological diseases in the clinic. It is a clinical syndrome caused by abnormal discharge of highly synchronized neurons in the brain caused by a variety of reasons, accompanying psychiatric and neurological comorbidities (1). Tuberous sclerosis complex (TSC) is a typical neurocutaneous syndrome characterized by cerebral and dermatological lesions, with hamartoma formation in multiple organ systems (3). TSC is typically characterized by severe neurodevelopmental disorders, which. Brain Proteomic Profiling of TSC generally include mental disabilities, autism, and other behavioral and psychiatric symptoms. These neurodevelopmental impairments were named TSC-associated neuropsychiatric disorders (TAND) (4). More than 70–80% of individuals with TSC have a history of seizures, which are often refractory to treatment, even with multiple antiepileptic drugs (6)
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