[Clinical and genetic analysis of a patient with Baraitser-Winter syndrome due to variant of ACTG1 gene].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Baraitser-Winter syndrome (BWS). METHODS: A BWS child who had sought medical attention at the Linyi People's Hospital on April 8, 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples were obtained from the child and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-and-6-month-old male, had typical clinical features of BWS including congenital non-myogenic ptosis, arched eyebrows, wide philtrum, and pointed chin. Neurological symptoms included microcephaly, developmental delay, epilepsy, and deafness. Cranial MRI revealed enlarged frontal lobes, decreased white matter, and hydrocephalus. WES has identified a heterozygous c.430G>A (p.Asn144Tyr) missense variant in the ACTG1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3_Moderate+PP4). CONCLUSION: The heterozygous c.430G>A (p.Asn144Tyr) missense variant of the ACTG1 gene probably underlay the pathogenesis of BWS in this child. Above finding has enriched the mutation spectrum of BWS-related genes and provided a basis for clinical diagnosis and genetic counseling.

[Genetic analysis and prenatal diagnosis of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 due to variants of PIGT gene].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents. METHODS: A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci. RESULTS: The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor. CONCLUSION: The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.

[Analysis of clinical phenotype and SCN1A gene variant in a pedigree affected with genetic epilepsy with febrile seizures].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members. RESULTS: The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%. CONCLUSION: The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.

Gender impacts on the correlations between nonalcoholic fatty liver disease and hypertension in a Chinese population aged 45-60 y.

No previous study has reported the association between nonalcoholic fatty liver disease (NAFLD) and the risk of hypertension in the Chinese population. Therefore, the aim of this study was to evaluate the relationship between NAFLD and hypertension in a middle-aged Chinese population. The study subject was (a group of) 1006 Chinese adults aged 45-60 y in Shandong Province who participated in the Weifang Nutrition and Health Survey (2014-2015). Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥ 9 0mmHg. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in women), no use of steatogenic medications within the past six months, no exposure to hepatotoxins, and no history of bariatric surgery. All anthropometric measurements and biochemical data were collected following standard protocols. Multivariate logistic regression analysis was used to identify the association between NAFLD and hypertension with adjustment of potential confounding variables. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting glucose, SBP, DBP, triglycerides (TG), serum uric acid (SUA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the prevalence of hypertension and NAFLD were significantly higher in males than in females (p < 0.05). Females had significantly higher levels of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). After adjusting for potential confounders, NAFLD was associated with an increased risk of hypertension in both male and female, with odds ratios (ORs) (95% CI) of 2.152 (1.324-3.498) and 2.133 (1.409-3.229), respectively. CONCLUSIONS: Our findings indicated that NAFLD was significantly associated with the risk of hypertension in males than in females. However, our findings also need to be confirmed in future prospective studies. ABBREVIATIONS: BMI: body mass index; WC: waist circumference; WHR: waist-hip ratio; SBP: systolic blood pressure; DBP: diastolic blood pressure; FG: fasting glucose; TG: triglycerides; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; SUA: serum uric acid; NAFLD: nonalcoholic fatty liver disease; LDL-C: low-density lipoprotein cholesterol; OR: odds ratio; CI: confidence interval; ALT: alanine aminotransferase; AST: aspartate aminotransferase.

Survey of enterovirus infections from hand, foot and mouth disease outbreak in China, 2009.

BACKGROUND: In China, a rapid expansion of Hand, foot, and mouth disease (HFMD) outbreaks has occurred since 2004 and HFMD has become an important issue for China. However, people are still only concerned with human enterovirus 71(HEV-71) and coxsackie virus A16 (CV-A16). Much of what is known about the other enterovirus infections relies on fractional evidence and old epidemic data, with little knowledge concerning their distribution. To alert potential threatens of the other enteroviruses, our study genetically characterized specimens from different regions of China and yielded novel information concerning the circulating and phylogenetic characteristics of enteroviral strains from HFMD cases. FINDINGS: A total of 301 clinical throat swabs were randomly obtained from patients suffering from HFMD from the southern, northern and central regions of China during outbreaks in 2009. 266 of 301 (88.4%) HFMD cases were found positive for HEV and seven genotypes, HEV-71, CV-A16, -B5, -A4, -A6, -A10, and -A12, were detected. CONCLUSIONS: The HFMD pathogen compositions in the different regions of China were significantly different. HFMD epidemics might persist for a long time in China due to the multiple pathogen compositions, the enteroviral characteristic of recombination and co-infection, the ever-increasing travel and migration and the deficiency of effective vaccine. Our study deserves the attention on HFMD control and vaccine development.

Atorvastatin Treatment for Atrial Fibrillation Reduces Serum High-Sensitivity C-Reactive Protein Levels.

We investigated whether serum hs-CRP levels predict the efficacy of atrial fibrillation (AF) treated with atorvastatin. Bibliographic databases were exhaustively searched for studies relevant to the research topic. Newcastle-Ottawa Scale (NOS) criteria, combined with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), were applied for study quality assessment. Our meta-analysis identified seven cohort studies (2006~2013), providing information on the change in serum hs-CRP levels in AF patients receiving atorvastatin therapy. After atorvastatin treatment, hs-CRP level in AF patients decreased significantly (SMD = 1.02, 95% CI: 0.58-1.47, P < 0.001). Subgroup analysis by country and hs-CRP detection methods suggested a negative relationship between atorvastatin treatment and hs-CRP levels among Chinese AF patients (SMD = 1.34, 95% CI: 1.00-1.69, P < 0.001) and by using ELISA method (SMD = 1.11, 95% CI: 0.51-1.71, P < 0.001), but not among Turkish population and using INA method (all P > 0.05). Egger's test showed no publication bias (P = 0.450). hs-CRP was clearly lowered in AF patients treated with atorvastatin, which may be helpful in the choice of statin agents for AF treatment. However, longer follow-ups are necessary to assess the clinical value of lowering hs-CRP in the clinical setting of AF treatment outcomes.

Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.

BACKGROUND: Enterovirus 71 (EV71) infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD). This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity. METHODOLOGY: Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined. PRINCIPAL FINDINGS: Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1) GM-CSF, MIP-1ß, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2) G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3) IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4) FACS analysis revealed that the frequency of CD19(+)HLADR(+) mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.