Targeted gene sanger sequencing should remain the first-tier genetic test for children suspected to have the five common X-linked inborn errors of immunity

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott–Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.The Hong Kong Society for Relief of Disabled Children and Jeffrey Modell Foundation.http://www.frontiersin.org/Immunologyam2023Paediatrics and Child Healt

Quantitative Characterization of Tumor Proximity to Stem Cell Niches: Implications on Recurrence and Survival in GBM Patients

PurposeEmerging evidence has linked glioblastoma multiforme (GBM) recurrence and survival to stem cell niches (SCNs). However, the traditional tumor-ventricle distance is insufficiently powered for an accurate prediction. We aimed to use a novel inverse distance map for improved prediction.Methods and materialsTwo T1-magnetic resonance imaging data sets were included for a total of 237 preoperative scans for prognostic stratification and 55 follow-up scans for recurrent pattern identification. SCN, including the subventricular zone (SVZ) and subgranular zone (SGZ), were manually defined on a standard template. A proximity map was generated using the summed inverse distances to all SCN voxels. The mean and maximum proximity scores (PSm-SCN and PSmax-SCN) were calculated for each primary/recurrent tumor, deformably transformed into the template. The prognostic capacity of proximity score (PS)-derived metrics was assessed using Cox regression and log-rank tests. To evaluate the impact of SCNs on recurrence patterns, we performed group comparisons of PS-derived metrics between the primary and recurrent tumors. For comparison, the same analyses were conducted on PS derived from SVZ alone and traditional edge/center-to-ventricle metrics.ResultsAmong all SCN-derived features, PSm-SCN was the strongest survival predictor (P < .0001). PSmax-SCN was the best in risk stratification, using either evenly sorted (P = .0001) or k-means clustering methods (P = .0045). PS metrics based on SVZ only also correlated with overall survival and risk stratification, but to a lesser degree of significance. In contrast, edge/center-to-ventricle metrics showed weak to no prediction capacities in either task. Moreover, PSm-SCN,PSm-SVZ, and center-to-ventricle metrics revealed a significantly closer SCN distribution of recurrence than primary tumors.ConclusionsWe introduced a novel inverse distance-based metric to comprehensively capture the anatomic relationship between GBM tumors and SCN zones. The derived metrics outperformed traditional edge or center distance-based measurements in overall survival prediction, risk stratification, and recurrent pattern differentiation. Our results reveal the potential role of SGZ in recurrence aside from SVZ

Gastroenteritis Outbreaks Caused by Norovirus GII.17, Guangdong Province, China, 2014–2015

In the past decade, the most prevalent norovirus genotype causing viral gastroenteritis outbreaks worldwide, including China, has been GII.4. In winter 2014–15, norovirus outbreaks in Guangdong, China, increased. Sequence analysis indicated that 82% of the outbreaks were caused by a norovirus GII.17 variant