Li Gao | PubMed Health

PubMed2026

Emergence of two novel HIV-1 Circulating Recombinant Forms (CRF190_0708 and CRF191_0708): molecular characterization and clinical insights from a five-year study in Yunnan, China.

BACKGROUND: To characterize HIV-1 molecular epidemiology and identify novel circulating recombinant forms (CRFs) among antiretroviral therapy (ART)-naïve heterosexuals in Yunnan, China, and evaluate their clinical impact. METHODS: This study examined 636 HIV-1 pol sequences to analyze genetic diversity, pretreatment drug resistance (PDR), and transmission networks. Near full-length genomes were obtained to identify and characterize novel recombinants, with their evolutionary history inferred by Bayesian analysis. Co-receptor tropism was predicted, and the five-year clinical outcomes (including immune reconstitution and virologic response) of patients infected with the novel CRFs were compared. RESULTS: The most prevalent type identified was CRF08_BC, accounting for 50.16% of cases. The prevalence of drug resistance was 5.97% (38/636), with the K103N mutation being the most common. An analysis of transmission networks revealed that 52.2% (272/521) of clusters were associated with CRF07_BC and CRF08_BC. Two novel second-generation CRFs were identified: CRF190_0708, with an estimated time to the most recent common ancestor (tMRCA) of 1998.9, and CRF191_0708, with a more recent tMRCA ranging from 2009.5 to 2011.6. During the five-year follow-up period, viral rebound was observed in 7 patients in the CRF190_0708 group and in 1 patient in the CRF191_0708 group. Drug-resistance mutations (M184V and K103N) were detected in a subset of rebound cases in the CRF190_0708 group. CONCLUSIONS: This study identifies two novel HIV-1 recombinants, CRF190_0708 and CRF191_0708, highlighting ongoing viral evolution in Yunnan. Preliminary findings suggest possible clinical differences, warranting further investigation. Continued molecular surveillance is needed. TRIAL REGISTRATION: The clinical study was registered at ClinicalTrials.gov under the identifier NCT03852849. The date of registration was March 22, 2019.

Adult↗

PubMed2025

Genetic analysis of four cases of Poirier Bienvenu neurodevelopmental syndrome associated with CSNK2B variant.

BACKGROUND: CSNK2B deficiency underlies the pathogenesis of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). In this study, we present four cases of pediatric seizures caused by de novo variants in CSNK2B, with the aim to reinforce the clinical and variant data pertaining to early genetic factors associated with epilepsy. METHODS: Trio whole exome sequencing were used to detect variants in the proband and her family members, and bioinformatics annotation was performed for the variant. Sanger sequencing and CSNK2B cDNA sequencing were employed to ascertain the carrier status of additional family members and evaluate the potential impact of variants on splicing. RESULTS: All four cases presented with epilepsy as the initial manifestation, accompanied by global developmental delay, particularly in language and motor developmental delay. Cases 1, 3 and 4 exhibited full-scale tonic-clonic seizures, while case 2 displayed myoclonic and typical absence seizures. Furthermore, case 2 demonstrated delayed growth and development compared to age-matched peers. No abnormality was detected in the head magnetic resonance imaging (MRI). Genetic analysis revealed novel heterozygous variants in the CSNK2B gene in all four cases, including c.175 + 1G > A, c.73-2A > G, c.291 + 1G > A and c.481delA. In case 2, reverse transcription analysis of CSNK2B mRNA revealed the retention of the 3' end sequence of Intron 2 and deletion of the 5' end sequence of Exon 3. In treatment, four case received a combination of one to three types of antiseizure medication and rehabilitation training individually. Case 1 continued to experience seizures to varying degrees, while cases 2-4 demonstrated effective seizure control. Overall motor and intellectual development improved in all four cases, however, there was slow recovery in language function. CONCLUSION: This study elucidates the molecular etiology of epilepsy in four cases with POBINDS and expands the mutational spectrum of pathogenic variants in the CSNK2B, highlighting their impact on splicing. The highly genetic heterogeneous phenotype of POBINDS relies on the detection of pathogenic variants in CSNK2B. Conventional antiseizure medication effectively control seizures, while rehabilitation treatment can significantly improve intelligence and motor function to varying degrees; however, language recovery tends to be relatively slow.

Humans↗