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Background Rett syndrome (RTT) is a severe neurodevelopmental disorder mainly affecting females. One of the main clinical manifestations is hand stereotypies, which is presumed to based on dysfunction rather than on structural impairment. Reflex interictal discharge precipitated by tapping-lips in electroencephalogram (EEG) is a rare phenomenon among RTT. Case presentation We firstly reported a case of RTT concerning interictal reflex discharge precipitated by tapping- lips. The child, female, 5 years old, presented with a significant regression in motor development and language skills. She almost always tapped the lips with the right hand and stopped only when was interrupted. Her EEG results displayed extensive low amplitude fast wave could be elicited by lightly and slowly- rhythm tapping lips and multifocal bilateral discharges could be precipitated by relatively stronger and quicker rhythm action. It was when the movement stopped that corresponding discharges immediately disappeared. Besides, the reflex discharges were not precipitated by tapping- lips using observer’s hand at the certain tempo and intensity. The hand stereotypies did not respond to antiepileptic drugs. Conclusions Tapping- lips may be a somatosensory stimulation to precipitate interictal discharges in RTT, which may provide another idea to enrich the insight on hand stereotypies of RTT.

The tumor microenvironment (TME) has been a major focus of research in recent years as a crucial factor in the development and progression of bladder cancer. Unfortunately, the precise composition of TME, particularly the immunological and stromal components, remains unknown. In this work, we downloaded the RNA-seq expression profiles and somatic mutation data of 433 bladder cancer cases from The Cancer Genome Atlas (TCGA) and then employed a comprehensive bioinformatics approach to evaluate them. Firstly, the expression profiles were used to predict the scores and then the content of immune and stromal cells via the estimate package in R software. We then identified differentially expressed genes (DEGs) and differentially mutated genes (DMGs) according to the high-stromal score cohort and low-stromal score cohort. Finally, fibroblast growth factor receptor 3 (FGFR3) was the main differentially mutated gene in bladder carcinoma that we discovered after conducting a cross-study on DEGs and DMGs. Follow-up investigation revealed that FGFR3, whose expression correlated inversely with cancer progression stage, appeared to be a protective factor in bladder cancer. The method of Gene Set Enrichment Analysis (GSEA) was employed to, respectively, interpret the expression data of FGFR3 in high and low expression lists. We observed that the genes in the low FGFR3 expression list were strongly enriched in the biological processes associated with transplantation and cell adhesion, suggesting the possible role of FGFR3 in predicting TME metastasis status in bladder cancer. Therefore, this study is aimed at investigating whether FGFR3 is promising as a biomarker of TME remodeling to explain underlying mechanisms involved in tumorigenesis and metastasis, which may help to make decisions on treatments for bladder cancer.

Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported.Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. Sanger sequencing was used to validate the variants identified in the siblings and their parents. In vitro functional study was performed.Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. However, the actual genotype-phenotype relationship needs more study.Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity.

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