OBJECTIVE: To delineate the clinical and genetic features of a Chinese girl harboring a rare de novo variant of SYNGAP1 associated with Mental retardation, autosomal dominant 5 (MRD5), and to conduct a comprehensive genotype-phenotype correlation analysis within the Chinese population through an extensive literature review. METHODS: A 5-year-old girl presenting with seizures without an obvious cause was enrolled in September 2020. Genomic DNA was extracted from the patient and her parents. Whole exome sequencing (WES) was performed on the proband to identify suspected pathogenic variants based on her clinical phenotype. Sanger sequencing was used for validation, followed by bioinformatic analysis of the variant. Additionally, data from 54 previously reported Chinese cases with SYNGAP1 variants were integrated to summarize the distribution of variant types and clinical characteristics. Ethical approval was obtained from the Ethics Committee of Kunming Children's Hospital (Ethics No.: 2021-03-055-K01). RESULTS: WES identified a heterozygous nonsense variant, SYNGAP1 c.725G>A (p.Trp242*), in the proband. Sanger sequencing confirmed it was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2). Based on the clinical manifestations, the patient was diagnosed with MRD5. Bioinformatic analysis suggested that this variant introduces a premature stop codon at tryptophan 242, disrupting the PH domain and leading to the loss of the C2, Ras-GAP, and C-terminal domains. The pooled analysis of Chinese cases revealed that nonsense (38.2%) and frameshift (36.4%) variants were the predominant types. Intellectual disability/developmental delay was present in 100.0% of patients, epilepsy in 83.6%, and autism spectrum disorder in 41.3%. The incidence of epilepsy differed significantly among variant types (P = 0.045). Exons 8 and 15 were identified as mutation hotspots. CONCLUSION This study has identified a SYNGAP1 c.725G>A variant in the Chinese population and confirmed it as a potential cause of MRD5, which expanded the mutational spectrum of this disorder.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; ras GTPase-Activating Proteins/genetics* ; Phenotype ; Exome Sequencing ; Genetic Association Studies

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

Objective:To analyze the epidemic characteristics and trends of newly reported HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture (Dehong Prefecture) of Yunnan Province, China, from 2000 to 2023, and provide evidence for formμlating AIDS prevention and control measures for the Burmese living in Dehong.Methods:The data were obtained from the Chinese Disease Control and Prevention Information System. The distribution of HIV-infected people with different population characteristics was analyzed, and the Joinpoint regression model was used to analyze the temporal trend of crude detection rate in different genders, ethnicities, and ages.Results:From 2000 to 2023, 24 989 newly HIV infections were reported in Dehong Prefecture, of which 14 594 (58.4%) were Chinese and 10 395 (41.6%) were Burmese. Compared with Chinese, Burmese women (32.9%, 3 416/10 395), those aged 20-29 (40.9%, 4 248/10 395), and Jingpo people (26.7%, 2 773/10 395) accounted for a higher proportion. The new diagnosis rate of Chinese nationals increased from 1.0/10 000 in 2000 to 15.4/10 000 in 2004, and then showed a downward trend, falling to 1.2/10 000 in 2023. Among them, compared with other age groups, Dai and other ethnic groups and women, the new diagnosis rate among 20-49 age group, Jingpo and men were relatively higher, at 1.7/10 000, 2.3/10 000 and 1.3/10 000 respectively. Regarding the method of detection, the Chinese HIV-infected people were mainly detected by key population testing (35.7%), while the Burmese HIV-infected people by key population testing (28.9%) and physical examination for entry-exit personnel (25.3%). The transmission routes of both nationalities were mainly heterosexual transmission, but compared with Chinese HIV-infected persons, the proportion of Burmese infected persons through non-marital non-commercial transmission was relatively higher (66.4% vs. 60.6%). The proportion of Chinese nationals with a first CD4 +T lymphocyte (CD4) counts of <200 cells/μl (28.9%) was higher than that of Burmese nationals (19.8%). Conclusions:The rising trend of HIV infection among Chinese and Burmese people in Dehong Prefecture from 2000 to 2023 slowed down. The new diagnosis rate was higher in the 20-49 age group, Jingpo and men. Compared with Burmese HIV-infected people, the proportion of Chinese HIV-infected people with first CD4 counts <200 cells/μl was relatively higher. Comprehensive interventions should be further carried out for Myanmar nationals, and efforts should be made to expand testing for Chinese nationals.

A retrospective analysis was made on the clinical data of a child with Turnpenny-Fry syndrome who was treated in the Epilepsy Center of Kunming Children′s Hospital in January 2023 for developmental retardation and epileptic spasm.The child, a 1-year-and-4-month-old boy, had developmental retardation since birth and developed epileptic spasm at the age of 5 months.Physical examination and auxiliary examination showed distinct facial features, heart, bone and other developmental malformations.Electroencephalogram indicated hypsarrhythmia and epileptic spasm.The genetic test suggested the presence of c. 194C>T (p.Pro65Leu), a new heterozygous mutation in PCGF2 gene.The seizures were completely controlled with anti-seizure drugs.This child is the only case reported with infantile epileptic spasm as the main manifestation so far, expanding the understanding of the phenotype of the disease.

ObjectiveTo investigate the factors that influence the first CD4+T lymphocyte counts in newly reported HIV-infected cases aged 50 and above in Dehong Prefecture of Yunnan Province during 2016 to 2021， and to understand the patient immune status and disease progression so as to provide scientific basis for HIV prevention and control strategies in the future. MethodsData was collected from the national HIV/AIDS information system. Multivariate logistic regression was used for the analysis of factors affecting the first CD4+T lymphocyte counts. ResultsA total of 642 cases of HIV infection were newly reported， among them， 571 cases had CD4+T lymphocyte counts and 200 cases （35.03%） had CD4+T lymphocyte counts <200 cells·μL^-1. Patients who were in the 50-59 age group， male， divorced or widowed， and less educated were more likely to have CD4+T lymphocyte counts <200 cells·μL^-1. Compared with active testing consultants， forced reeducation through labor or drug rehabilitation cases were less likely to have CD4+T lymphocyte counts <200 cells·μL^-1. ConclusionThere is no obvious upward trend in newly reported HIV infected persons aged 50 years and above in Dehong Prefecture during 2016 to 2021. However， the situation of CD4+T lymphocyte counts <200 cells·μL^-1 is still serious. Attention should be paid to the key groups： male， Chinese nationality， farmers， Han nationality， married or divorced， junior high school education or below， and heterosexual transmission. It is necessary to strengthen the intervention in people aged 50 and above and improve the detection efficiency.

ObjectiveTo understand the epidemiological characteristics and trends of sexually transmitted diseases （STDs） in Dehong Prefecture， Yunnan Province from 2010 to 2022， so as to provide a basis for the prevention and control of STDs in Dehong Prefecture. MethodsThe 2010‒2022 epidemic cards of STD cases in Dehong Prefecture were downloaded from the China Disease Control and Prevention Information System， and descriptive analysis of the incidence rate and demographic characteristics by disease type was conducted. The syphilis screening data of various populations in Dehong Prefecture between 2014 and 2022 were obtained from the National STD Control and Management Information System， and the syphilis positivity rates of key populations were calculated. ResultsA total of 18 225 STD cases were reported in Dehong Prefecture from 2010 to 2022， and the reported incidence rate increased from 17.1/10⁵ in 2010 to 172.0/10⁵ in 2022， showing an increasing trend （χ²_trend=42.9， P<0.001）. The number of reported cases of gonorrhea， syphilis， condyloma acuminatum， genital chlamydia infection， and genital herpes were 7 801 （42.8%）， 4 563 （25.0%）， 3 462 （18.8%）， 1 660 （9.1%）， and 775 （4.3%）， respectively. The majority of the reported STD cases were males （12 336 cases， 67.7%）， young adults aged 15 to <45 years （15 839 cases， 87.2%）， and farmers （9 230 cases， 50.7%）. The elderly group aged 65 years and over accounted for 10.5% of syphilis cases. Among different types of key populations， the highest syphilis positivity rate was found among men who have sex with men （10.1%）， followed by STD clinic attendees （8.1%）， and the syphilis positivity rates among clandestine prostitutes， voluntary counseling and testing population， drug addicts， and drug rehabilitation center/re-education through labor center population were 2.2%， 1.6%， 1.4%， and 1.3%， respectively. ConclusionFrom 2010 to 2022， the STD epidemic in Dehong Prefecture showed a rapidly increasing trend， with a higher incidence of gonorrhea and syphilis， and a higher syphilis positivity rate among men who have sex with men， drug addicts， clandestine prostitutes， and STD clinic patients. In the future， publicity， education and behavioral interventions for these groups should be strengthened to reduce the prevalence and transmission of STDs.

ObjectiveTo determine the characteristics， viral load and immunological status of HIV-infected persons and their spouses who became HIV-positive， and the reasons for HIV seroconversion in 55 HIV discordant couples in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunan Province. MethodsData on the 55 couples meeting the criteria of having a previously positive spouse were retrieved from the AIDS Integrated Prevention and Control Data Information System of the China Disease Control and Prevention Information System during 2015-2021. General socio-demographic information， age at diagnosis， exposure history， CD4⁺T lymphocyte count， and antiviral treatment were collected. Descriptive analysis and chi-square test were used to compare the distribution of pre-HIV-positive spouses and their HIV seroconverted spouses. ResultsA total of 55 spouses from HIV discordant couples had HIV seroconversion. Of them， 72.7% （40/55） of pre-HIV-positive spouses were husbands. The most recent CD4⁺T lymphocyte count in the pre-HIV-positive spouses was （328.31±246.27） cells·μL^-1 at the time of diagnosis of their seroconverted spouses， of which 36.3% （20/55） had a CD4⁺T lymphocyte count of less than 200 cells·μL^-1. Furthermore， of those pre-HIV-positive spouses with low CD4⁺T lymphocyte count， 45.0% （9/20） had an undetectable viral load， 15.0% （3/20） <400 copies·mL^-1， and 25.0%（5/20） ≥400 copies·mL^-1. Additionally， 16.4% （9/55） of the pre-HIV-positive spouses did not have a viral load test. The main reasons for HIV seroconversion among HIV-negative spouses in the discordant couples were poor condom use， poor compliance with antiviral therapy， and treatment discontinuation. ConclusionThe follow-up management of HIV discordant couples should be strengthened in Dehong Prefecture， especially the monitoring of viral load levels and immunological status of pre-HIV-positive spouses， to improve their compliance with antiviral therapy and reduce treatment discontinuation， which would effectively prevent and control HIV transmission between spouses.

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.

ObjectiveTo determine the characteristics and influencing factors of hepatitis C virus （HCV） co-infection among HIV concordant couples in Dehong Prefecture. MethodsUsing the data of newly reported HIV concordant couples in Dehong Prefecture from 2016 to 2019， we collected the demographic characteristics， exposure history， and HCV infection to determine the characteristics of HCV co-infection among HIV concordant couples. ResultsAmong the 160 HIV concordant couples included in the study， 46 （28.8%） males and 14 （8.8%） females were co-infected with HCV. The prevalence of HIV-HCV co-infection was higher among the male spouses who were diagnosed less than 40， Jingpo ethnic， Burmese， illiteracy， farmers， and intravenous drug users. In contrast， the prevalence of HIV-HCV co-infection was higher among the female spouses who were diagnosed less than 40， Jingpo ethnic， and Burmese. Logistic regression analysis among male spouses showed that the Jingpo ethnic and intravenous drug users had higher risk of HCV co-infection. ConclusionHIV concordant couples in Dehong Prefecture have high prevalence of HIV-HCV co-infection. Effective intervention strategies should be developed based on ethnic-specific factors and exposure characteristics among male and female spouses of HIV concordant couples.

ObjectiveTo investigate the demographic characteristics， high-risk behavior and first CD4⁺T cell（CD4 cell） counts among newly reported HIV-infected Burmese in Dehong Dai Jingpo Autonomous Prefecture （Dehong Prefecture） from 2019 to 2020. MethodsA cross-sectional survey was conducted among newly reported HIV-infected Burmese cases in Dehong Prefecture from 2019 to 2020 to collect related information and measure their first CD4 cell counts. ResultsAmong 1 228 HIV-infected Burmese cases， 846 （68.9%） were males and 382 （31.1%） were females； 445 （36.2%） were from Kachin， and 210（17.1%） were from Shan. Of them， 960 cases （78.2%） had participated in the first CD4 cell counts testing， and 405 cases （42.2%） had a first CD4 cell counts <350 cells·μL^-1. In the multivariable logistic regression analysis， age ≥30 years （adjusted OR=1.44， 95%CI： 1.07‒1.92） and history of illicit drug use in Myanmar （adjusted OR=0.41， 95%CI： 0.21‒0.79） were independently associated with first CD4 cell counts <350 cells·μL^-1. ConclusionThe first CD4 cell counts are generally low among newly reported HIV-infected Burmese in Dehong Prefecture， especially those aged ≥ 30 years and with a history of intravenous drug use in Myanmar. Therefore， early detection of HIV infection should be strengthened for timely intervention and treatment management among Burmese.