title: Novel DOCK8 gene mutations lead to absence of protein expression in patients with hyper-IgE syndrome.
abstract: Autosomal recessive hyper-immunoglobulin E syndrome (AR-HIES) caused by DOCK8 defects is characterized by recurrent elevated serum IgE level, elevated peripheral eosinophil count, severe atopy, recurrent viral and bacterial infections, and early-onset malignancy. The clinical, genetic, and immunologic characteristics of DOCK8 mutations in Chinese patients have not been characterized in detail. In this research, we screened seven Chinese candidate patients for mutations within the DOCK8 gene and identified three large novel homozygous deletions and four novel point mutations by targeted deep sequencing. The homozygous deletions displayed autosomal recessive inheritance, and the point mutations were sporadic. Absence of DOCK8 protein was confirmed using flow cytometry and western blotting. Besides the typical clinical features and immunologic impairments of DIDS, proliferation of lymphocytes, cytotoxic function of NK cells, and expression of IL-10 in regulatory B cells were severely impaired in DOCK8 mutant patients which may be associated with abnormal immune responses in DIDS. These findings will contribute to the early diagnosis and treatment of DOCK8 patients.
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: An
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Chaohong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Dai
authors.affiliation: Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Daoqi
authors.initials: D
authors.lastname: Wu
authors.affiliation: Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
authors.affiliation: Division of Immunology, Fujian Provincial Hospital, Fujian, 350001, China. 241811191@qq.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. zhaoxd530@aliyun.com.|Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. zhaoxd530@aliyun.com.|Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China. zhaoxd530@aliyun.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002681:China; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007589:Job Syndrome / Q000175:diagnosis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D016753:Interleukin-10
keywords: DOCK8; Flow cytometry; Hyper-IgE syndrome; Immune function; Mutation; Targeted deep sequencing