RÉSUMÉ
Objective:To analyze the clinical characteristics of adult-onset patients with familial neuronal intranuclear inclusion disease (NIID).Methods:The clinical data of 3 patients with familial NIID genetically diagnosed in Department of Neurology, Sixth Affiliated Hospital of Guangzhou Medical University in August 2021, January 2022, and August 2022 were collected. Their clinical manifestations, imaging features, pathological features, Notch2 N-terminal-like C ( NOTCH2NLC) gene mutation characteristics, treatment methods and prognoses were summarized retrospectively. Results:The age of these 3 patients was 73, 67, and 65 years, and the onset age was 68, 64, and 56 years, respectively. The clinical manifestations are highly heterogeneous. In patient 1, the nervous centralis, peripheral nerves and autonomic nerves were involved, appearing dementia, epilepsy, Parkinson's syndrome, muscle weakness and uremia; in patient 2, only the nervous centralis were involved, presenting symptoms of Parkinson's syndrome; in patient 3, peripheral nerves and autonomic nerves were involved, prominently presenting with repeated vomiting. Skull diffusion weighted imaging (DWI) showed asymmetric high signal at the dermo-medullary junction in 3 patients. Acidophilic inclusion bodies in some sudoriferous duct epithelial cells, and vascular endothelial nucleus were found in the skin biopsy of 2 patients. All 3 patients completed NOTCH2NL gene test, and all had GGC repeat amplification mutations with mutation frequency>134. These 3 patients were mainly treated symptomatically, and the disease was still progressed gradually. Conclusion:The clinical manifestations of familial NIID are highly heterogeneous; skull MRI characteristic changes and skin biopsy can help to diagnose NIID and NOTCH2NL gene detection can diagnose NIID.
RÉSUMÉ
Objective To observe the expression of calcium/calAulin kinaseⅡα (CaMKⅡα) in the brain tissues of fragile X mental retardation 1 (FMR1) gene knockout (KO) mice to investigate whether CaMKⅡα is regulated by fragile X mental retardation protein (FMRP).Methods According to the gene types of the FVB inbred mice identified by PCR,20 mice were divided into KO group and WT (wide type) group (n=10).The subcellular distribution and expression of CaMKⅡα were observed by immunohistochemical staining; the mean optical density (A) values of immunostaining signal of CaMKⅡα in various brain regions,including the motor cortex,temporal cortex,amygdala,hypothalamus and hippocampus,were determined by IBAS 2.0 image-analyzed system.Results CaMKⅡα immunoreactive cells were abundantly found in all brain subregions of KO and WT mice; especial positive signal was noted in the proximal processes of neurons,so as to those in the dendrite; week signcal was observed in the axon.No distributional difference was found between KO and WT mice.As compared with those in the WT mice,the A values were distinctly increased in each brain region of KO mice with significant differences (P＜0.05).Conclusion The increased expression of CaMKⅡα in the brain tissues of FMR1 knockout mice hints that CaMKⅡα participates in the course of the fragile X syndrome,and FMRP may negatively regulate the expression of CaMKⅡα in physiological condition.