ABSTRACT
Objective@#To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants.@*Methods@#The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children′s Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. The clinical features and gene test results were analyzed retrospectively.@*Results@#Data of 9 patients (4 boys and 5 girls) diagnosed as myoclonus dystonia syndrome caused by SGCE variants were collected. The onset age ranged from 1 year to 3 years and 2 months. The first symptom was myoclonus in 4 cases, while dystonia in the remaining 5 cases. In the course of the disease, 9 cases had myoclonus and 8 had dystonia. Myoclonic jerks were characterized by involuntary jerks in both upper limbs in 8 patients. Six patients had involuntary jerks of lower limbs, resulting in gait instability or even falling. The myoclonus was exacerbated during the fine motor activities, emotional stress or fatigue. Dystonia was characterized by abnormal gait, including 5 cases with right leg dystonia, and 3 cases with the left leg dystonia. Three probands had a positive family history. Intellectual development was normal in all cases. There was no obvious abnormality in video-electroencephalogram (EEG) during both ictal and interictal periods. Electromyography (EMG) and brain magnetic resonance imaging (MRI) of 9 patients were normal. Nine patients carried SGCE gene variants, including 3 frame shift variants, 2 nonsense variants, 2 missense variants, 1 fragment deletion variant and 1 splice site variant. Seven variants were inherited paternally, and 2 variants were de novo. Madopar was used in 8 patients, and nitrazepam in 4 patients, leading to the decrease in the myoclonus jerks and improvement of gait in 6 and 2 patients, respectively.@*Conclusions@#SGCE gene variants can cause myoclonus dystonia syndrome. The onset of the disease may occur at infancy or preschool age, with either myoclonic jerks or dystonia as the initial symptom. Non-epileptic myoclonus is the prominent symptom, with upper limb mainly involved. Most of the patients have the accompanying symptoms of dystonia, and some of them may have spontaneous symptom relief. SGCE gene is imprinted maternally, and the inherited variants of SGCE are paternal in origin.
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Objective To establish a mouse model of intrauterine malnutrition to investigate the growth characters and the DNA methylation level of H19 of the offspring. Methods The pregnancy ICR mice were randomly divided into the food restricted group and the control group. The food eaten by each pregnant mouse every day was monitored from d0. 5 to d12. 5. The food restricted pregnancy mice were given half amount food of the daily consumption during d0. 5-d12. 5. The mice in control group were given the normal food. The pregnant mice of both groups of were given normal food after delivery. The number, birth weight and sex ratio of the offspring were calculated. Furthermore, the body weight of the offspring was monitored at different growth stages. The oocytes of female offspring mice were obtained to detect the DNA methylation level of H19. Results (1) Compared to normal feeding pregnant mice, mice with food restricted were small and less active, and even some of them were died before delivery. The incidence of premature birth was significantly increased (P ＜0. 05). The number of abortion, stillbirth pregnant mice in the food restriction group were more than that in the control group, but the difference was not statistically significant (P ＞ 0. 05). (2) There was no significant difference in the number of offspring between pregnancy mice with food restricted or normal food (P ＞ 0. 05). As well as the number of male offspring between the two groups (P ＞ 0. 05). However, the offspring of the food restricted pregnant mice showed significant low birth weight (P ＜ 0. 05). (3) At the age of 3 weeks, there was still a low body weight in the offspring of the food restricted pregnant mice, but the difference had no significant difference between groups (P ＞ 0. 05). After weaning at 3 weeks, the offspring of food restricted pregnant mice began the catch-up growth. At the age of 6 weeks, the body weight of offspring of food restricted pregnant mice was higher than that of the normal offspring, but the difference was not statistically significant (P ＞ 0. 05). During the period of 6-8 weeks, the weight of offspring of normal feed pregnancy mice was increased slowly. But the body weight of food restriction offspring mice was increased rapidly. At the age of 8 weeks, the body weight of offspring of food restricted group was significantly higher than that in control group (P ＜ 0. 05). (4) The methylation level of H19 in oocyte from offspring of food restricted pregnancy mice was normal. Conclusion Food restriction at pregnancy period not only affect the outcome of pregnancy, but also increased the rate of premature birth. The offspring of food restriction pregnancy mice showed low birth weight. Until the age of 6 weeks, the offspring of food restriction pregnancy mice had lower body weight compared with the offspring with normal feeding pregnancy mice. The offspring of food restriction pregnancy mice demonstrated obesity at 8 weeks. But the H19 methylation levels of oocytes from offspring of pregnancy mice with food restriction was normal.
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Objective By comparing the methylation status of imprinted gene H19 in three different quality spermatozoa and the methylation status of the embryos after the combination of spermatozoa, the sperm methylation status in the ART technique was preliminarily explored with the postnatal embryo methylation.Methods In this study, a total of 91 spermatozoa and 91 low－quality embryos were collected from IVF－ET in the First People's Hospital of Yunnan Province. Among them, sperm samples were divided into three groups according to the sperm concentration parameter in the WHO fourth edition,then the relationship between different quality spermatozoa and postnatal embryo methylation were analyzed.Results The abnormality rate of H19 methylation status in group B was significantly higher than that of the sperm group and the embryo group.Conclusions The abnormalities of H19 methylation mainly concentrated in the abnormal parameters of spermatozoa,suggesting that the abnormal state was related to the decrease of sperm quality;Through IVF, ICSI fertilized embryos have the same proportion of the corresponding abnormal state with no significant difference; Abnormal sperm embryos did not show abnormality, which may be related to the self－repair function of the embryo itself.