[Analysis of a child with developmental disorder and epilepsy due to a homozygous variant of SLC25A12 gene].

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay and epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c.115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+PM3_Supporting+PP3_Moderate+PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. CONCLUSION: The homozygous c.115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.

Molecular epidemiology of Streptococcus pneumoniae isolated from pediatric community-acquired pneumonia in pre-conjugate vaccine era in Western China.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is one of the most common pathogens which can cause morbidity and mortality in pediatric infections worldwide. This study aimed to describe the phenotypic and molecular characteristics of community-acquired pneumonia (CAP)-causing S. pneumoniae recovered from children in Western China. METHODS: We retrospectively enrolled pediatric patients younger than 5 years diagnosed with CAP. All 419 S. pneumoniae isolates were tested for antibiotic susceptibility, serotypes, virulence genes, resistance genes, and sequence types. The potential relationships between molecular characteristics were tested by correspondence analysis. RESULTS: Most of S. pneumoniae isolates were resistant to erythromycin, tetracycline, clindamycin and trimethoprim-sulfamethoxazole, with 93.8% isolates classified as multidrug resistant. The dominant STs were ST271 (30.8%) and ST320 (12.2%), while the prevailing serotypes were 19F (46.8%), 6B (11.5%), 23F (9.5%) and 19A (9.3%). The coverage rates of PCV-7 and PCV-13 were 73.03% and 86.16%, while the coverage rates of PCV13 among children aged < 1 year and 1-2 years were high in 93.18% and 93.62%. We also observed that CC271 expressed more of mef (A/E), lytA, rlrA and sipA than non-CC271 isolates. Moreover, there were strong corresponding relationships between molecular characteristics. CONCLUSIONS: The high coverage rate of PCV13 suggests the necessity of introducing the PCV13 vaccine in Western China. Our findings underscore the value of monitoring multiple molecular characteristics to provide new guidance for developing future pneumococcal vaccines.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive diseases in China: a meta-analysis.

BACKGROUND: To summarize information about invasive pneumococcal disease (IPD) among children in mainland China. METHODS: Sixteen eligible studies were included in this systematic review and the random effect model was used to estimate the pool prevalence of IPD. RESULTS: The most predominant serotypes circulating in children were 19F (27.7, 95% confidence interval (95% CI): 17.7-37.6%), 19A (21.2%, 16.4-26.1%), 14 (16.5%, 12.8-20.1%), 6B (8.6%, 5.2-10.8%) and 23F (7.3%, 5.2-9.5%). The serotype coverage of the available pneumococcal conjugate vaccines PCV7, PCV10, and PCV13 was 60.8% (52.5-69.4%), 65.1% (57.7-72.4%), and 90.0% (87.1-92.8%), respectively. The pooled antibiotic resistance rates of Streptococcus pneumoniae revealed a resistance to penicillin prevalence rate of 32.0% (12.1-51.9%). Approximately 94.4% (90.7-98.1%) and 92.3% (87.4-97.3%) of isolates were resistant to erythromycin and clindamycin. eBURST analysis revealed great diversity among isolates, with 102 sequence types (STs) for 365 isolates. The major predominant clonal complexes (CCs) were CC271 (43.6%, 159/365), CC876 (13.4%, 49/365), CC81 (5.2%, 19/365), and CC90 (4.1%, 15/365). Long-term and regional surveillance of S. pneumoniae is necessary. CONCLUSIONS: Based on our pooled results showing that PCV13 coverage of the reported serotypes was 90% and that most serotypes contributed to the distribution of antibiotic-resistant isolates, implementation of PCV13 into the Chinese Expanded Program on Immunizations (EPI) would achieve health benefits in Chinese children.