Clinical And Immunological Characteristics Of Gene Mutation With IKBKG Or STAT5B

PART Ⅰ CLINICAL AND IMMUNOLOGICALCHARACTERISTICS OF A CASE WITH NEMO-IDObjective: Performed an investigation of the clinical,genetic,and immunological characteristics of a 7-year-old boy who presented with recurrent infections and lymphadenectasis,but no responsible gene was identified in his next-generation sequencing report.The aim was to highlight the necessity of analyzing the raw data of high-throughput sequencing when the gene report was inconsistent with patient’s clinical manifestations.Methods: A patient without responsible gene identified in his gene report but presenting with typical immunodeficiencies was enrolled.Gathered clinical data and raw data of high-throughput sequencing to identify the defected gene,and took flow cytometry for immunologic screening,western blot for detecting the NEMO expression,and further functional analysis like lymphocyte proliferation test to evaluate immunologic phenotype of the patient.Result: A heterozygous G > A substitution located in exon 9 splicing site(21819)was found in the patient and his asymptomatic mother.This variant will result in false mRNA slicing and significantly reduced expression of NEMO protein.As compared with that of healthy parents,B cell proliferation was dramatically impaired in the patient.Conclusion: This is the first report of a NEMO-ID patient with splice site mutation of IKBKG gene in China.For patients who suffered from recurrent infections,even without typical clinical symptoms of ectodermal dysplasia,NEMO-ID should be considered.For further diagnosis,next-generation sequencing and immunologic screening should be done.Rigorous analysis of the sequence’s raw data can be helpful for the final diagnosis due to pseudogenes,which may interfere with analysis of high-throughput sequencing.PART ⅡCLINICAL AND IMMUNOLOGICAL CHARACTERISTICS OF A CASE WITH STAT5 B MUTATIONObjective: To investigated the clinical,genetic,and immunological characteristics of a patient with a spontaneous missense mutation in STAT5 B gene,implying to provide evidences for the hereditary mode of STAT5 B deficiency,as well as provide more information about diagnosis and treatment of this rare disease.Methods: A patient with a missense mutation of STAT5 B gene was enrolled.Performed an analysis of clinical information and immunologic phenotype including the proportion of peripheral blood lymphocyte subsets and the proportion of Treg.Sanger sequencing was used for verifying the patient’s genetic mutation and Western blot for evaluating the phosphorylation function of STAT5 B in patients.Result: The main clinical manifestations of the STAT5B-deficient patient included recurrent diarrhea,pulmonary infections,low gamma-globulinemia,lymphadenectasis,and lymphocytopenia.A STAT5 B heterozygous mutation was detected by whole exome sequencing(WES).Analysis of lymphocyte subsets showed an increased proportion of Th2 cells and a decreased proportion of Treg.In addition,the phosphorylation of STAT5 B was defected in patient.Conclusion: This is the first report of the patient with heterozygous STAT5 B gene mutation in China.Genotype and phenotype were both corresponding with STAT5B-deficient patients reported in published papers.Clinical data and immunological characteristics were analyzed,intending toprovide reliable information for diagnosis and treatment of the disease.It also suggested that dominant inhibition or other factors may be involved in the occurrence and development of this disease.