Genetic analysis of developmental and epileptic encephalopathy caused by novel biallelic SZT2 gene mutations in three Chinese Han infants: a case series and literature review.

BACKGROUND: Developmental and epileptic encephalopathy (DEE) exhibits phenotypic and genetic heterogeneity. Biallelic variants of the SZT2 gene can lead to DEE18, of which few cases have been reported. This study aimed to analyze the potential pathogenic factors in three cases of DEE18. METHODS: Trio-whole exome sequencing and crystal structure simulation analysis were performed, along with a literature review of DEE18 cases. RESULTS: All three patients had compound heterozygous variants in the SZT2 gene (patient 1, c.2887A > G/c.7970G > A; patient 2, c.3508A > G/c.7936C > T; and patient 3, c.2489G > T/c.8640_8641insC). The variants were predicted to have structural effects on the protein. Particularly, c.3508A > G/p.Ser1170Gly may lead to impaired binding of SZT2 to GATOR1, potentially resulting in the overactivation of the mTORC1 signaling pathway, causing seizures. Through the literature review, we observed that 27 patients with DEE had different degrees of intellectual and developmental disorders (DDs), and the variants leading to protein truncation cause severe DD and refractory epilepsy. Therefore, the phenotypic severity of patients may be related to the residual activity of variant SZT2 protein. CONCLUSION: We provide recently developed knowledge on the DEE18 genotype-phenotype spectrum and suggest that gene detection is of great value for the accurate diagnosis of patients with early-onset epilepsy. Further research is required for the development of individualized interventions for patients with DEE.

[Effects of bacterial lysates and all trans-retinoic acid on airway inflammation in asthmatic mice].

OBJECTIVE: To observe the effects of bacterial lysates (OM-85BV) and all trans-retinoic acid (ATRA) on airway inflammation in asthmatic mice, and to investigate the immunoregulatory mechanism of OM-85BV and ATRA for airway inflammation in asthmatic mice. METHODS: Forty female BALB/c mice were randomly divided into five groups: normal control, model, OM-85BV, ATRA, and OM-85BV+ATRA. A bronchial asthma model was established by intraperitoneal injection of ovalbumin (OVA) for sensitization and aerosol challenge in all mice except those in the normal control group. On days 25-34, before aerosol challenge, the model, OM-85BV, ATRA, and OM-85BV+ATRA groups were given normal saline, OM-85BV, ATRA, and OM-85BV+ATRA respectively by gavage. Normal saline was used instead for sensitization, challenge, and pretreatment before challenge in the normal control group. These mice were anesthetized and dissected at 24-48 hours after the final challenge. Bronchoalveolar lavage fluid (BALF) was collected from the right lung to measure the levels of interleukin-10 (IL-10) and interleukin-17 (IL-17) by ELISA. The left lung was collected to observe histopathological changes by hematoxylin-eosin staining. The relative expression of ROR-γT mRNA was measured by quantitative real-time PCR. RESULTS: Compared with the normal control group, the model group showed contraction of the bronchial cavity, increased bronchial secretions, and a large number of infiltrating inflammatory cells around the bronchi and alveolar walls, as well as a significantly reduced level of IL-10 (P<0.05) and significantly increased levels of IL-17 and ROR-γT mRNA (P<0.05). Compared with the model group, the OM-85BV, ATRA, and OM-85BV+ATRA groups showed a significant reduction in infiltrating inflammatory cells around the bronchi and alveolar walls; the OM-85BV group showed a significant increase in the level of IL-10 in BALF (P<0.05) and significant reductions in the levels of IL-17 and ROR-γT mRNA (P<0.05); the ATRA group showed significant reductions in the levels of IL-17 and ROR-γT mRNA (P<0.05). Compared with the OM-85BV group, the OM-85BV+ATRA group had significantly increased relative expression of ROR-γT mRNA (P<0.05). Compared with the ATRA group, the OM-85BV+ATRA group had significantly increased levels of IL-10 and IL-17 in BALF (P<0.05). CONCLUSIONS: Both OM-85BV and ATRA can reduce respiratory inflammation in asthmatic mice. However, a combination of the two drugs does not have a better effect than them used alone.