Self-limiting epilepsy syndrome（SeLES）can be classified into two types based on age of onset：one occurring in the neonatal to infant period and the other in the childhood period.These diseases can exhibit complete remission within a specific age range，or be completely controlled with anti-seizure drugs.Children with SeLES typically have normal cognition or only mild cognitive impairment.In recent years，advancements in genetic testing technology have led to a better understanding of the genetic etiologies of SeLES，offering more possibilities for precision treatment.This article aims to explore the role of genetic factors in SeLES，providing reference for the diagnosis，precise drug selection，and prognosis of this type of hereditary epilepsy syndrome，in order to provide theoretical support for the long-term management of patients，and improve their quality of life.

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome. METHODS: A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation. RESULTS: The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant. CONCLUSION The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.
Female ; Humans ; East Asian People ; Intellectual Disability/genetics* ; Mutation ; Myopia/genetics* ; Pedigree ; Vesicular Transport Proteins/genetics* ; Child, Preschool ; Child

Objective To study the pinoresinol diglucoside (PDG) on gene regulation role of ESF-1 cells in collagen secretion, to reveal PDG repair mechanisms on scalded skin.Methods The cells cultured in vitro were divided into the control group, the estradiol group and the three different PDG doses groups. The concentration of the high, medium and low dose groups were 100, 10, 1μmol/L, and that of estradiol group were 10-3μmol/L. The activity of proliferation was detected by MTT. Then collagen type I (Col I), collagen typeⅢ (ColⅢ), tissue inhibitors of metalloproteinase 1 (TIMP-1), tissue inhibitors of metalloproteinase 2 (TIMP-2) and matrix metalloproteinase 1 (MMP-1) expression levels of mRNA after administration of cells were detected by RT-PCR.Results Compared with the control group, the proliferation of ESF-1 cells (0.559 ± 0.027, 0.552 ± 0.034vs. 0.489 ± 0.027,P<0.05) in the estradiol and medium-dose PDG was significantly higher. The expression level of mRNA of ColⅠ(0.958 ± 0.021, 0.929 ± 0.031, 0.916 ± 0.015vs. 0.844 ± 0.022), ColⅢ (0.783 ± 0.038, 0.918 ± 0.021, 0.855 ± 0.017vs. 0.678 ± 0.024), TIMP-1 (0.939 ± 0.025, 0.889 ± 0.036, 0.853 ±  0.015 vs. 0.780 ± 0.023), TIMP-2 (0.507 ± 0.024, 0.655 ± 0.037, 0.572 ± 0.025vs. 0.405 ± 0.062) in the estradiol, low-, medium-dose PDG groups were significantly higher than those in the control group (P<0.05 or P<0.01). Besides, the MMP-1 (0.343 ± 0.038, 0.407 ± 0.046, 0.435 ± 0.037vs.0.519 ± 0.041) mRNA expression level in the middle and low dose PDG groups significantly decrease (P<0.05 orP<0.01). Conclusions The PDG could enhance the activity of ESF-1 cell proliferation, increase the expression of related collagen and tissue inhibitor of metalloproteinases and inhibit that of matrix metalloproteinases to repair scalded skin.

Objective: To explore the utility of pharyngeal pH monitoring which positive standard is Ryan index in diagnosis of laryngopharyngeal reflux disease. Methods: In a retrospective study, clinical data of 590 patients who had symptoms laryngopharyngeal reflux disease from February 2016 to March 2017 were analyzed. All patients were received electronic laryngoscopy, assessment of reflux symptom index(RSI) and reflux finding score(RFS), and pharyngeal pH monitoring. SPSS 19.0 software was used to analyze the date. Results: There were 94 patients whose Ryan index were positive(15.93%). Among the 94 patients, 70 were positive during upright, 12 during supine and 12 during both upright and supine. There were 40 patients(6.78%)with pH decline events related to symptoms, while those Ryan index were normal. There were 536(90.85%), 417(70.68%), 233(39.49%) and 117(19.83%) patients with pH<6.5, pH<6.0, pH<5.5 and pH<5.0 events respectively. The positive rate of RSI, RFS, RSI and RFS, RSI or RFS were 44.24%, 16.78%, 7.12%, 53.90% respectively. The RFS score in Ryan index positive group was higher than that in Ryan index negative group[(8.2±2.4) vs (4.0±2.9), u=5.424, P<0.05], while the RSI score in Ryan index positive group was not statistically different from that in Ryan index negative group[(11.3±6.2) vs (12.7±5.8), t=1.247, P=0.167]. Conclusions Pharyngeal pH monitoring is an objective and non-invasive method which can reflect laryngopharyngeal reflux directly. However, with the Ryan index as a criterion for the diagnosis of laryngopharyngeal reflux disease, partial patients may be missed. Further studies are needed to obtain more accurate and objective laryngopharyngeal pH statistical index for diagnosis of laryngopharyngeal reflux disease.