De Novo mutation causing X-linked hyper-IgM syndrome: A family study in Taiwan

Yi-Chun Ma, Wen I. Lee, Shyh-Dar Shyur, Sheng-Chieh Lin, Li-Hsin Huang, Jiunn-Yi Wu

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8 Citations (Scopus)


X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder caused by mutations of the gene encoding the CD40 ligand (CD40L). It is characterized by recurrent infections with markedly decreased serum IgG, IgA and IgE levels but normal or elevated IgM levels. We report the clinical manifestations and complete immune studies in the first family with molecularly proven XHIM in Taiwan. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgA, and IgE were noted in his plasma specimen: IgM, 128 mg/dl; IgG, 18 mg/dl; IgA, 4 mg/dl); IgE, 1 IU/ml. Whole blood flow cytometry when he was 21 months old showed that only a small percentage (0.48%) of his in vitro-activated CD4+ T cells expressed CD40L. When he was 3 years old, repeated flow cytometry showed essentially the same result (0.4%), compared with his father's CD40L expression of over 85%. The patient's mother had moderately decreased CD40L expression (74.4%). Hyper-IgM syndrome was confirmed by CD40L mutation analysis in the boy, which revealed a Lys 96 stop (nucleotide A307T) in exon 2 of CD40L, with a truncated protein resulting in the loss of the entire TNF domain. His mother was a carrier and apparently the individual in whom the mutation originated. Eleven other family members, including the patient's father, sister, and grandmother, and the mother's sisters and their children, all had normal results on CD40L mutation analysis. The patient has remained without significant bacterial infection on a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, although he has had recurrent oral ulcers and neutropenia. Bone marrow transplantation is planned.
Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalAsian Pacific Journal of Allergy and Immunology
Issue number1
Publication statusPublished - 2005
Externally publishedYes


  • antibiotic agent
  • CD4 antigen
  • CD40 ligand
  • cotrimoxazole
  • immunoglobulin A
  • immunoglobulin E
  • immunoglobulin G
  • immunoglobulin M
  • tumor necrosis factor
  • adult
  • article
  • bacterial infection
  • blood sampling
  • bone marrow transplantation
  • case report
  • clinical feature
  • disease carrier
  • family study
  • female
  • flow cytometry
  • gene expression
  • gene mutation
  • human
  • hyperimmunoglobulinemia M
  • immune deficiency
  • immunoglobulin blood level
  • in vitro study
  • infant
  • male
  • mouth ulcer
  • mutational analysis
  • neutropenia
  • onset age
  • Pneumocystis pneumonia
  • pneumonia
  • protein domain
  • quantitative analysis
  • rare disease
  • recurrent infection
  • stop codon
  • T lymphocyte
  • Taiwan
  • X chromosome linkage
  • CD40 Ligand
  • Female
  • Genetic Diseases, X-Linked
  • Humans
  • Hypergammaglobulinemia
  • Immunoglobulin M
  • Infant
  • Killer Cells, Natural
  • Male
  • Mutation
  • Pneumonia


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