title: X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients.
abstract: Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the most frequent type, is caused by mutations in the CD40 ligand gene, and is regarded as a combined T and B immunodeficiency. We report an 18-year-old male who was diagnosed initially with hypogammaglobulinemia in infancy, but developed repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and bronchiectasis despite regular intravenous immunoglobulin replacement therapy. The patient died at age 18 years due to pneumonia and tension pneumothorax. Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L protein expression. Sequence analysis in the family confirmed a de novo mutation. The second case of 6-month-old male infant presented as Pneumocystis jiroveci pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was arranged in the second case.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hu-Yuan
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.affiliation: Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuan-Hua
authors.initials: KH
authors.lastname: Chu
authors.affiliation: Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, SAR, China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: yan0126@ms15.hinet.net.
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D023201:CD40 Ligand / Q000235:genetics*; D018389:Codon, Nonsense; D005091:Exons; D017809:Fatal Outcome; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000175:diagnosis* / Q000235:genetics*; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D009894:Opportunistic Infections / Q000453:epidemiology*; D017354:Point Mutation; D013624:Taiwan
chemical_list: D018389:Codon, Nonsense; D023201:CD40 Ligand