Hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder, characterized by eczema, recurrent skin and lung infections, and significantly elevated serum IgE level. It was previously diagnosed based on clinical manifestations and laboratory markers that were not specific to the disease. Recent studies have demonstrated that mutations in signal transducer and activator of transcription 3 (STAT3) cause the autosomal dominant or sporadic HIES, which make the disease definitively characterized at molecular level. Here, we reported a 3-year old Chinese boy with neonatal-onset rash and multiple serious Staphylococcus aureus infections including recurrent skin abscesses, liver abscess, sepsis, and destructive pulmonary infection (pneumonia, multiple pulmonary abscesses, pyopneumothorax, and finally, pneumatocele). Genetic study revealed a heterozygous mutation in exon 21 of STAT3 gene (g.66583 A > C, c.1970A > C) in the boy, which resulted in a substitution of tyrosine at the amino acid position 657 to serine (p.Y657S) in the Src homology 2 (SH2) domain of STAT3. Functional prediction with bioinformatics programs of the Sorting Intolerant from Tolerant (SIFT) and the Polymorphism Phenotyping (PolyPhen) reported “deleterious (SIFT score 0.02)” and “probably damaging (PSIC score difference 2.94)” values, respectively. Further study of family members revealed that neither his parents, nor his twin brother carried the mutation, indicating the mutation was likely to occur de novo in our patient. Conclusion: The mutation,p.Y657S,in SH2 domain of STAT3 is a disease-causing mutation in the boy with HIES.
Hyper-IgE syndrome Staphylococcal infection Liver abscess Pneumatocele The signal transducer and activator of transcription 3(STAT3)
Qiang Li has received a research funding from the Department of Science and Technology of Sichuan Province, China (No.2008JY0029-1). We deeply thank Professor Yu-lung Lau*, Professor Wen-wei Tu* and Dr.Koon-wing Chan* for their invaluable help (Qiang Li has received a 3-months training in molecular diagnosis of primary immunodeficiency disease in the Department of Paediatrics & Adolescent Medicine, Hong Kong University). We are also grateful to the patient and his parents for their cooperation.
*Department of Paediatrics & Adolescent Medicine, Hong Kong University.
Conflict of Interest Statement
Qiang Li has received research support from the Department of Science and Technology of Sichuan Province, China (No.2008JY0029-1). All authors declare that no actual or potential conflict of interest in relation to this article exists.
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