title: Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype.
abstract: OBJECTIVE
  Hyper IgM syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, defective class switch recombination and somatic hypermutation, are heterogeneous disorders with at least 6 distinct molecular defects, including the CD40 ligand (CD40L) and the nuclear factor κB essential modulator (NEMO, also known as IKKγ) genes (both X-linked), the CD40, activation-induced cytidine deaminase (AICDA or AID), uracil-DNA glycosylase genes (autosomal recessive) and IκBα (IKBA) (autosomal dominant). Our objective was to determine the molecular basis and clinical features of Taiwanese patients with the HIGM phenotype.
  
  
  METHODS
  Clinical manifestations and candidate genes were analyzed in a nationwide population-based study.
  
  
  RESULTS
  Among 14 patients (12 unrelated families) since 2003, 10 patents were identified (8 families) with CD40L mutations, including 2 novel deletions of "A" nucleotide (Del 347A and Del 366A), both frameshift and stop at the 127th location; 1 novel AID deletion mutation lack of the 37thAsp and 38th Ser; 1 ataxia-telangiectasia mutation; and 1 deletion of chromosome 1q42. An adult-onset patient with mutant (Thr254Met)CD40L had approximately 30% detectable affinity and therefore less severity. Memory B cells decreased in patients with CD40L and activation-induced cytidine deaminase mutations. Three mortalities encompassed renal cell carcinoma in 1 patient with (Tyr169Asn)CD40L, pneumothorax in 1 with (Tyr140Stop)CD40L and pneumonia after chemotherapy in an ataxia-telangiectasia patient. One patient without detectable genetic defects but normal lymphocyte proliferation resembled the mild form of common variable immune deficiency phenotype.
  
  
  CONCLUSIONS
  In contrast to those with AICDA mutation, small chromosome 1 q42 deletion and unknown genetic defect, the majority (10/14; 71.4%) with CD40L mutations except (Thr254Met) and an ataxia-telangiectasia patient had the severe form of HIGM phenotype.
authors.affiliation: From the *Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung Children's Hospital; †Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Chang Gung University College of Medicine and Children's Hospital, Taoyuan; ‡Department of Pediatrics, Chi Mei Hospital, Tainan; §Department of Pediatrics, Division of Hematology and Oncology, Chang Gung Children's Hospital; ¶Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan; ‖Department of Pediatrics, National Taiwan University Hospital; and **Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Yeh
authors.forename: Min-Jay
authors.initials: MJ
authors.lastname: Yang
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Lai
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Chen
authors.forename: Liang-Shiou
authors.initials: LS
authors.lastname: Ou
authors.forename: Tsung-Chieh
authors.initials: TC
authors.lastname: Yao
authors.forename: Syh-Jae
authors.initials: SJ
authors.lastname: Lin
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Chen
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Yu
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Shyh-Dar
authors.initials: SD
authors.lastname: Shyur
mesh_terms: D023201:CD40 Ligand / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000235:genetics* / Q000473:pathology*; D007223:Infant; D008297:Male; D009154:Mutation; D017384:Sequence Deletion; D013624:Taiwan
chemical_list: D023201:CD40 Ligand