Importance:Aicardi-Goutières syndrome(AGS)is a rare genetic disorder mainly affecting the central nervous system and autoimmunity.However,research on AGS among Chinese patients is limited.Objective:To summarize t...Importance:Aicardi-Goutières syndrome(AGS)is a rare genetic disorder mainly affecting the central nervous system and autoimmunity.However,research on AGS among Chinese patients is limited.Objective:To summarize the neurologic phenotypes and genetic causes in pediatric AGS patients,providing insights for early recognition and diagnosis in the Chinese population.Methods:Clinical features and neuroimaging results of the patients diagnosed with AGS from Beijing Children’s Hospital between January 2018 and January 2022 were collected.Whole exome sequencing was used for genetic analysis.Results:A total of 15 patients was included,all presenting with various neurological symptoms,including developmental delay(100%),motor skill impairment(100%),language disability(78.6%),dystonia(93.3%),microcephaly(73.3%),sleep disorders(26.7%),regression(20.0%),vessel disease(6.7%),and epilepsy(6.7%).Neuroimaging revealed intracranial calcification(86.7%),cerebral atrophy(73.3%),and leukodystrophy(73.3%).Seven genes were identified,with TREX1 being the most common(40.0%,6/15),followed by IFIH1(20.0%,3/15).Variant c.294dupA(p.C99Mfs*3)was detected in four unrelated patients,accounting for 66.7%(4/6)patients with the TREX1 variant.A literature review showed that TREX1 gene mutations in 35.6%(21/59)of AGS patients among the Chinese population.Interpretation:Neurological symptoms are the most prevalent and severe presentation of AGS.Diagnosis may be considered when symptoms such as developmental delay,dystonia,microcephaly,brain calcification,and leukodystrophy emerge.TREX1 mutations are predominant in the Chinese population.展开更多
Anesthetics evoke a stress-response, upregulating heat shock genes. This neuroprotective response to proteotoxic stress represents preconditioning, a process by which neuronal tissue, previously exposed to anesthetics...Anesthetics evoke a stress-response, upregulating heat shock genes. This neuroprotective response to proteotoxic stress represents preconditioning, a process by which neuronal tissue, previously exposed to anesthetics, is protected against future insult. It presumes a sub-lethal injury, affecting protein unfolding. Our hypothesis is: preconditioning evokes molecular events that result in downstream changes that offer a selective advantage in terms of neuronal function. We focused on the neurobehavioral aspects which we neurophenotyped. Larval zebrafish were exposed to trifluoroethanol (TFE), an anesthetic mimetic, and tested for both individual and group behavioral markers of neuronal function. In bright/dark tests, we observed that TFE-exposed larvae spent more time in the dark area (typically an adult-like response) than control larvae. The response of TFE larvae to noise startle was directly opposite to that of controls. TFE larvae swam towards the source of the startle (into the bright zone), whereas control larvae swam away from the source of the startle (into the dark), typical of fear-response. The larvae also exhibited several differences in social behaviors, including synchronized schooling and shoaling behaviors. The TFE-group showed a greater number of synchronized events versus controls. The TFE-group also exhibited more shoaling events compared with controls. While the long-term effects have yet to be determined, these results shed light on the mechanism of anesthetic preconditioning. These complex zebrafish behaviors normally develop with age and therefore represent, in the TFE-exposed group, a pattern of accelerated maturation of neuronal function, which is the neurophenotype attributed to preconditioning.展开更多
文摘Importance:Aicardi-Goutières syndrome(AGS)is a rare genetic disorder mainly affecting the central nervous system and autoimmunity.However,research on AGS among Chinese patients is limited.Objective:To summarize the neurologic phenotypes and genetic causes in pediatric AGS patients,providing insights for early recognition and diagnosis in the Chinese population.Methods:Clinical features and neuroimaging results of the patients diagnosed with AGS from Beijing Children’s Hospital between January 2018 and January 2022 were collected.Whole exome sequencing was used for genetic analysis.Results:A total of 15 patients was included,all presenting with various neurological symptoms,including developmental delay(100%),motor skill impairment(100%),language disability(78.6%),dystonia(93.3%),microcephaly(73.3%),sleep disorders(26.7%),regression(20.0%),vessel disease(6.7%),and epilepsy(6.7%).Neuroimaging revealed intracranial calcification(86.7%),cerebral atrophy(73.3%),and leukodystrophy(73.3%).Seven genes were identified,with TREX1 being the most common(40.0%,6/15),followed by IFIH1(20.0%,3/15).Variant c.294dupA(p.C99Mfs*3)was detected in four unrelated patients,accounting for 66.7%(4/6)patients with the TREX1 variant.A literature review showed that TREX1 gene mutations in 35.6%(21/59)of AGS patients among the Chinese population.Interpretation:Neurological symptoms are the most prevalent and severe presentation of AGS.Diagnosis may be considered when symptoms such as developmental delay,dystonia,microcephaly,brain calcification,and leukodystrophy emerge.TREX1 mutations are predominant in the Chinese population.
文摘Anesthetics evoke a stress-response, upregulating heat shock genes. This neuroprotective response to proteotoxic stress represents preconditioning, a process by which neuronal tissue, previously exposed to anesthetics, is protected against future insult. It presumes a sub-lethal injury, affecting protein unfolding. Our hypothesis is: preconditioning evokes molecular events that result in downstream changes that offer a selective advantage in terms of neuronal function. We focused on the neurobehavioral aspects which we neurophenotyped. Larval zebrafish were exposed to trifluoroethanol (TFE), an anesthetic mimetic, and tested for both individual and group behavioral markers of neuronal function. In bright/dark tests, we observed that TFE-exposed larvae spent more time in the dark area (typically an adult-like response) than control larvae. The response of TFE larvae to noise startle was directly opposite to that of controls. TFE larvae swam towards the source of the startle (into the bright zone), whereas control larvae swam away from the source of the startle (into the dark), typical of fear-response. The larvae also exhibited several differences in social behaviors, including synchronized schooling and shoaling behaviors. The TFE-group showed a greater number of synchronized events versus controls. The TFE-group also exhibited more shoaling events compared with controls. While the long-term effects have yet to be determined, these results shed light on the mechanism of anesthetic preconditioning. These complex zebrafish behaviors normally develop with age and therefore represent, in the TFE-exposed group, a pattern of accelerated maturation of neuronal function, which is the neurophenotype attributed to preconditioning.
