Objective To evaluate the application value of whole exome sequencing (WES) in diagnosis of NDDs (neuro-developmental disorders) children.Metheod WES was used for the diagnosis of 35 unexplained NDD children, which admitted to the outpatient and ward of Children′s hospital affiliated to Capital institute of pediatric from November 2015 to November 2016.These children′s clinical data was collected detailedly.Using bioinformatics software tools combining with patient′s phenotype, the candidate genetic/genomic variants of these patients were identified from WES data.The final pathogenicity of genetic/genomic variants was interpreted according to the guideline of the American College of Medical Genetics and Genomics (ACMG), meanwhile, the variants validation and co-separation analysis in the parents and their family members were performed by Sanger sequencing, real time-PCR and multiplex ligation-dependent probe amplification (MLPA).Results 14 pathogenic single nucleotide variants (SNVs) and three pathogenic copy number variations (CNVs) were detected in the 35 NDD children, the detection rate in this study is 48.6%.Among the 14 pathogenic SNVs, 11 of them are the definite NDD-related genes according to OMIM database (such as CHARGE syndrome, Wiedemann-Steiner syndrome, Cockayne syndrome, etc.), and six of them are de novo (6/11, 54.6%).Three pathogenic CNVs were identified from WES data, including two microduplications and one microdeletion.Meanwhile, a female child carrying a frame shift mutation in MECP2 was found and the germline mosaicism with low-frequency mutation of this site (8.4%) was confirmed by his father's sperm.Conclusions The diagnosis rate of WES in NDDs children is 48.6% in our small-sample study.In addition to pathogenic/likely pathogenic SNVs, CNVs can be detected successfully from WES data, which effectively improved the diagnosis yield in NDDs children.

Objective:To investigate the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma(NDMM)with thrombocytopenia.Methods:Clinical data of 529 patients with NDMM admitted to The Second Hospital of Shanxi Medical University between January 2012 and December 2021 were retrospectively analyzed.The patients were categorized into thrombocytopenia and nor-mal platelet count groups based on their platelet count levels.Results:A total of 529 patients with NDMM were included in this study,with 108(20.42%)patients in the thrombocytopenia group.The median progression-free survival(mPFS)was 30.64 months(95%confidence in-terval[CI]:23.43-37.85)in the thrombocytopenia group,which was shorter than that in the normal platelet count group(41.39 months[95%CI:37.37-45.39],P=0.002).The median overall survival(mOS)was 40.59 months(95%CI:30.61-50.57)in the thrombocytopenia group,which was shorter than that in the normal platelet count group(60.92 months[95%CI:54.54-67.29],P<0.001).Multivariate Cox regression analysis identified thrombocytopenia as a risk factor for OS in patients with NDMM(HR=1.238[95%CI:1.16-1.952],P=0.03).Conclusions:The prognosis of patients with NDMM with thrombocytopenia was worse than that of patients with NDMM who had normal platelet levels.Thrombocytopenia may serve as a poor prognostic indicator for NDMM.