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04, median event free survival 22.8 vs. 5.6 months; P=0.04, median OS 124 vs. 22.5 months). Conclusions We thus propose that hyperactive Ras signaling confers inferior survival in high-risk pediatric acute leukemia and that Ras pathways should be molecularly characterized to inform clinical decision making and to identify patients for experimental clinical trials and RAS-targeted therapy. 2020 Translational Pediatrics. All rights reserved.Background This study aims to investigate the efficacy and safety of umbilical cord blood transplantation (UCBT) without serotherapy for treating children with leukocyte adhesion deficiency type I (LAD-I). Methods Clinical characteristics and data of five children with LAD-I who underwent UCBT at our hospital between September 2016 and September 2018 were retrospectively analyzed. Results Five (two boys and three girls) patients with LAD-I were included. The median age at UCBT was 9 months (range, 8 to 32 months). The same myeloablative conditioning regimen was administered for each patient and included busulfan, fludarabine, and cyclophosphamide. HLA matching of patients and umbilical cord blood was 8/10 to 10/10. The median dose of total nucleated cells (TNC) infused was 10.2×107/kg (range, 4.5×107 to 20.6×107/kg) and the median dose of CD34+ cells was 3.2×105/kg (range, 1.9×105 to 5.7×105/kg). The median time of neutrophil engraftment was 20 days (range, 13 to 28 days). The median time of platelet engraftment was 36 days (range, 32 to 56 days). All patients received complete donor chimerism (CDC). Four of the five patients developed grade II-IV acute graft-versus-host disease (GvHD). The median follow-up time after transplantation was 19 months (range, 8 to 38 months). Four of the patients survived and achieved complete clinical remission. The other patient died of bronchiolitis obliterans 8 months after UCBT. Conclusions UCBT is an effective treatment method for LAD-I patients. Also, severe LAD-I patients should undergo stem cell transplantation as early as possible. click here 2020 Translational Pediatrics. All rights reserved.Background FLNC encodes actin-binding protein and is mainly concentrated in skeletal and cardiac muscle. Mutations in FLNC were found in cardiomyopathies. To date, studies on FLNC-cardiomyopathies have mainly been reported in adults. There are limited studies that have investigated FLNC variants in pediatric patients with cardiomyopathies. Methods We summarized the patients who carried rare variants of FLNC from May 2016 to May 2019 in the Center for Molecular Medicine, Children's Hospital of Fudan University, from clinical exome sequencing data. Results A total of 5 patients with FLNC rare variants were included. Of them, 3 were male and 2 were female. The median age was 3 months (range from 19 days to 30 months). A1186V was a known pathogenic variant reported in pediatric patients with cardiomyopathy (PMID 29858533), and the other four variants were novel. In the four novel variants, there are one splicing (c.2265+4del) and three missense (p.R441I, p.C1639Y, and p.A2648S). Two patients (patients 1 and 3) were diagnosed with restrictive cardiomyopathy, two patients (patients 2 and 5) were diagnosed with dilated cardiomyopathy, and one patient (patient 4) was diagnosed with arrhythmia. Conclusions All five patients have survived to date. In summary, FLNC rare variants identified by clinical exome sequencing provide genetic evidence to make early diagnosis of cardiomyopathy in infant patients. 2020 Translational Pediatrics. All rights reserved.Background This study aimed to evaluate the clinical value of virtual touch tissue imaging quantification (VTIQ) in the diagnosis and treatment of congenital muscular torticollis (CMT) in children. Methods Sixty-two CMT children treated in the clinics of our hospital were collected, and then 62 CMT children treated with manipulation massage were followed up; 23 CMT children receiving surgery in the same period served as controls. Conventional ultrasonography and VTIQ were performed at bilateral sternocleidomastoid muscles (SCM), and the shear wave velocity (SWV) was measured. Results In 62 patients and 23 controls, the average SWV of affected SCM was higher than the contralateral SCM. The difference was statistically significant (P0.05). The SWV of SCM after treatment was lower than before treatment. The difference was statistically significant (P less then 0.01). The SWV of affected SCM in 23 controls was higher than the affected SCM in 62 patients before massage. The difference was statistically significant (P less then 0.01). Conclusions VTIQ is helpful for the diagnosis of CMT in children and can also be employed for the monitoring of therapeutic effect. 2020 Translational Pediatrics. All rights reserved.Background Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, while relapse and refractory ALL remains a leading cause of death in children. However, paired ALL samples of initial diagnosis and relapse subjected to next-generation sequencing (NGS) could construct clonal lineage changes, and help to explore the key issues in the evolutionary process of tumor clones. Therefore, we aim to analyze gene alterations during the initial diagnosis and relapse of ALL patients and to explore the underlying mechanism. Methods Targeted exome sequencing technology was used to detect molecular characteristic of initial diagnosis and relapse of ALL in 12 pediatric patients. Clinical features, treatment response, prognostic factors and genetic features were analyzed. Results In our 12 paired samples, 75% of pre-B-cell acute lymphoblastic leukemia (B-ALL) patients had alterations in the Ras pathway (NRAS, KRAS, NF1, and EPOR), and Ras mutation are very common in patients with ALL relapse. TP53 mutations mainly existed in the primary clones and occurred at the initial diagnosis and relapse of ALL. Relapse-associated genes such as NT5C2 and CREBBP were observed in patients with ALL relapse; however, all patients included in this study had gene abnormalities in the Ras pathway, and NT5C2 and CREBBP genes may collaboratively promote ALL relapse. Conclusions Among the 12 ALL patients, Ras pathway mutations are common in ALL relapse and may be associated with other recurrence-related genes alterations. The study with paired samples could improve the understanding of ALL relapse. 2020 Translational Pediatrics. All rights reserved.