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.

Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.

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.
Humans ; Female ; Child ; Pregnancy ; Child, Preschool ; Muscle Hypotonia/genetics* ; Prenatal Diagnosis ; Computational Biology ; Epileptic Syndromes ; Facies

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

Objective:To study the infection of human rhinovirus, respiratory syncytial virus and human adenovirus in Jinan from April 2018 to March 2019, and analyze epidemiological characteristics of human adenovirus.Methods:All of 1969 nasopharyngeal swabs were collected from hospitalized patients with acute respiratory tract infections in The Fourth People’s Hospital of Jinan, Qilu Children′s Hospital of Shandong University, Peoples Hospital of Zhangqiu District from April 2018 to March 2019, fluorescence quantitative PCR was used to detect the positive rate of human rhinovirus, respiratory syncytial virus and human adenovirus. Seven adenovirus positive samples were isolated and examined by sequencing, then we determined adenovirus type, constructed gene phylogenetic trees for analysis.Results:Of the 1969 samples, 242 were positive, the total positive rate was 12.30% (242/1969), the positive rate was 3.00% (59/1969) for rhinovirus, 6.30% (124/1969) for respiratory syncytial virus (RSV), and 3.86% (76/1969) for adenovirus. There was no significant difference in the detective rate of rhinovirus in different age groups (Fisher′s exact test value =8.376, P=0.720), the positive rates of RSV and adenovirus in different age groups was statistically significant ( χ2=19.28, 12.16; P=0.001, 0.016). There was a statistically significant difference in the positive rate of adenovirus between different sexes ( χ2=14.33, P<0.001), and there was no statistically significant difference in the positive rate of rhinovirus and RSV between males and females ( χ2=0.30, 2.90, P=0.862, 0.089). Comparing the positive rates of viral nucleic acid in different months, we found that the positive rate of rhinovirus, RSV and adenovirus separately reached the highest in October, December and November (8.61%, 26.50% and 8.84%). We constructed a gene phylogenetic tree after seven positive samples of adenoviruses were sequenced, by the molecular typing method we detected that seven adenovirus-positive samples were all HAdV-2 type. Conclusions:By comparing the epidemiological trends of human rhinovirus, RSV and human adenovirus in Jinan from April 2018 to March 2019 in different ages, genders, and months, providing reference basis for the early prevention and clinical treatment of acute respiratory tract infection.

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.
Epilepsy/genetics* ; Humans ; NAV1.1 Voltage-Gated Sodium Channel/genetics* ; Pedigree ; Phenotype ; Seizures, Febrile/genetics*

Objective:To understand the infection rate of Coronavirus Disease 2019 (COVID-19) in close contacts in Shandong province and explore the risk factors of infection.Methods:All data from close contacts of 2019 novel coronavirus (2019-nCoV) infected persons in Shandong province were collected for descriptive epidemiological analysis, and risk factors were analyzed by logistic regression.Results:Up to March 6, 2020, a total of 15 702 close contacts had been reported in Shandong province, of whom 321 cases were infected with 2019-nCoV, with an infection rate of 2.04%. Among all the factors, the top five with the highest infection rate were close relatives (13.39%), frequent contact (9.58%), working/living/studying in the same room (7.54%), two or more contact cases (4.58%), and over 60 years old (3.10%). Single-factor analysis showed that exposure to two or more cases, over 60 years old, close relatives with cases, frequent contact and working/living/studying in the same room were the risk factors for infection in close contacts. Multivariate analysis showed that exposure to two or more cases ( OR=2.510, 95% CI: 1.843-3.417), 30~60 year old group ( OR=1.513, 95% CI: 1.141-2.007), frequent exposure group ( OR=20.025, 95% CI: 14.625-27.419), working/living/learning in the same room ( OR=2.406, 95% CI: 1.385-4.182) and medical institution exposure ( OR=2.366, 95% CI: 1.149-4.871) were risk factors of infection in close contacts. Conclusions:Tracking and managing close contacts was an important measure to control the COVID-19 epidemic situation, and reducing crowd concentration, keeping a proper social distance and taking effective protection were effective measures to control 2019-nCoV infection.

Objective: To understand the viral spectrum of influenza-like illness (ILI), Shandong province during 2013-2014. Methods: The data of 36 ILI outbreaks were collected and analyzed. Multiple respiratory pathogens were detected with RT-PCR in pharynx swab specimens. Results: Totally, 35 outbreaks occurred in winter and spring, and dispersed in 12 cities; 27 outbreaks happened in primary and secondary schools. Many of the outbreaks, 17 (47.2%), were caused by influenza virus type B (FluB), followed by FluA H1 and H3, 5 (13.8%) outbreaks, respectively. Mixed infection caused 7 outbreaks. Totally 437 samples were collected, with 235 (53.8%) positive specimens, in which FluB was mostly detected, 142 (32.5%). Except Flu, parainfluenza virus type 2 (PIV2) was the most frequently detected, followed by coronavirus (CoV). The constituent ratio of FluB under 15 years of age was the highest, such as CoV in 25-59 years old group and FluA H1 in others groups. Conclusions ILI outbreaks occurred mostly in primary and secondary schools. Virus was the main pathogen, with the dominant strains of FluB. However, the dominant strain in different age groups was different.

Objective To explore the clinical features of mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS) syndrome in fratemal twins brothers.Methods The clinical data,the results of laboratory examinations,electroencephalogram (EEG),imaging,and gene detection,and the process of diagnosis and treatment were retrospectively analyzed the fraternal twin brothers with MELAS syndrome.Results The proband,a 7-year-old male,had intermittent headaches,vomit and twitching at onset.He suffered from exercise intolerance,fatigue,accompanied by short stature and hairy.The fasting blood lactic acid level was increased.Multiple video EEG showed the slowdown of background activity.Head MRI showed recurrent lesions with the characteristics of migration and variation.The point mutation rate of mtDNA A3243G was 34.7％.The diagnosis of MELAS was confirmed.At the same time,his fraternal twin brother was screened and found that his point mutation rate of A3243G was 30.0％.Although there was no clinical symptom at that time,he was onset with convulsion after 3 years.Conclusions Gene detection and family screening are helpful for the early diagnosis of MELAS.The mutation rate of A3243G is very high,which can cause an early onset and serious clinical symptoms.

Objective]To discuss the effect of sciatic nerve injury on the expressions of tumor necrosis factor-alpha(TNF-α), interleukin-1β(IL-1β)and interleukin-10(IL-10)in anterior cingulate cortex(ACC),and further to explain their roles resided in the development of neuropathic pain.[Method]With use of the methods of behavioral test,western blot and immunohistochemistry, we examine the effects of spared sciatic nerve injury(SNI)on the expressions of TNF-α,IL-1β,and IL-10 in ACC,and observe the effect of the neutralizing antibody of TNF-α,IL-1β on the rat mechanical allodynia.[Result]In present experiment ,SNI increased the protein levels of TNF-α,IL-10,but not IL-1β in ACC. Increased TNF-α-IR and IL-10-IR in ACC is located in neurons ,but not astrocytes and microglia at 7 d following L5-VRT. Pre-treatment with anti-TNFα antibody but not anti-IL-1βantibody into ACC significantly increased the rat paw withdrawal threshold to von Frey hairs.[Conclusion]These data suggested that the increased TNF-αin ACC neurons might be responsible for the development of neuropathic pain.