Genetic Linkage of Hyper-IgE Syndrome to Chromosome 4

Grimbacher, Bodo; Schäffer, Alejandro A.; Holland, Steven M.; Davis, Joie; Gallin, John I.; Malech, Harry L.; Atkinson, T. Prescott; Belohradsky, Bernd H.; Buckley, Rebecca H.; Cossu, Fausto; Español, Teresa; Garty, Ben Zion; Matamoros, N.; Myers, Lawrence E.; Nelson, Robert P.; Ochs, Hans D.; Renner, Eleonore D.; Wellinghausen, Nele; Puck, Jennifer M.

doi:10.1086/302547

Cited by 349 publications

(277 citation statements)

References 32 publications

Supporting

Mentioning

255

Contrasting

Unclassified

Order By: Relevance

“…TSLP is known to initiate typical IgE-and T H 2 cell-dependent allergic diseases through its effects on dendritic cells, whereas its ability to potently stimulate MCs might contribute to the T cell-and IgE-independent allergic inflammation. 4,5 In agreement with a previous study, 6 here we show that primary human BSM cells from nonasthmatic donors (commercially 5 with or without antibody to TNF or isotype control (10 mg/mL each). Data are representative of 4 experiments.…”

Section: To the Editorsupporting

confidence: 91%

See 1 more Smart Citation

A novel mutation in the linker domain of the signal transducer and activator of transcription 3 gene, p.Lys531Glu, in hyper-IgE syndrome

Kim

Shin

et al. 2009

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

A novel mutation in the linker domain of the signal transducer and activator of transcription 3 gene, p.Lys531Glu, in hyper-IgE syndrome To the Editor:Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by eczema, recurrent abscesses, pneumonia with pneumatocele, and an increased serum IgE level. Most cases are sporadic, but both autosomal dominant and autosomal recessive forms have been described. 1 Recently, mutations in the signal transducer and activator of transcription factor 3 gene (STAT3) have been determined to be the cause of autosomal dominant HIES. 2,3 Most STAT3 mutations were located in the DNA-binding domain or Src homology 2 domain, whereas missense mutations were also found in the transactivation domain downstream of the Src homology 2 domain. [2][3][4] Here we report the first STAT3 mutation in the linker domain of the protein in a boy with HIES.A 5-year-old Korean boy was admitted because of fever, cough, and otorrhea for a week. His parents were not consanguineous. He had no remarkable perinatal problems and had been vaccinated as scheduled. He had a history of atopic dermatitis since 6 months of age. Ingestion of eggs and milk had been restricted until 43 months of age, when he passed the open challenge test. Of note, past medical history also revealed recurrent infections, including multiple episodes of oral candidiasis. He was treated with antibiotics for an abscess on the scalp caused by group A b-hemolytic Streptococcus species at 4 months of age. He had a history of 3 hospitalizations for pneumonia without pneumatocele. Suppurative cervical lymphadenitis caused by Staphylococcus aureus, which occurred at 18 months of age, was successfully treated with incision, drainage, and antibiotics, but it recurred several times afterward. At 4 years of age, tympanostomy tubes were inserted in the eardrums bilaterally for recurrent otitis media caused by Streptococcus pneumoniae. Family history revealed no members with relevant allergic or immunologic diseases.On physical examination, his height was 104.6 cm (10th percentile), and his weight was 17 kg (25th percentile). He had coarse facial features with a low hairline and hypertelorism and genu valgum. A whitish plaque was found on the soft palate. The left external auditory canal was wet, and the tympanostomy tube was not in situ in his left ear. A 1.0 3 1.0 cm, hard, tender lymph node was palpable in the left supraclavicular area. Fine crackles were heard on both lung fields, and his skin was slightly dry. Complete blood cell counts demonstrated a normal total eosinophil count (<400 cells/mL), although his eosinophil count had been up to 7000 cells/mL at 6 months of age. Plain chest radiographic analysis demonstrated bilateral peribronchial infiltrates, and Haemophilus influenzae was isolated from sputum culture. The serum IgE level was increased at 3980 IU/mL. Results of other immunologic studies, such as serum immunoglobulin level measurement and the nitroblue tetrazolium test, were normal. Lymphocyte subset ana...

show abstract

Section: To the Editorsupporting

confidence: 91%

“…His National Institutes of Health score was 45 points (''probably affected''; Table I). 5 Written informed consent was obtained from the parents for molecular genetic studies for STAT3 mutations. Direct sequencing analysis of the STAT3 gene was performed with genomic DNA isolated from peripheral blood leukocytes.…”

Section: To the Editormentioning

confidence: 99%

A novel mutation in the linker domain of the signal transducer and activator of transcription 3 gene, p.Lys531Glu, in hyper-IgE syndrome

Kim

Shin

et al. 2009

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…The genomic loci with possible linkage to OG-sensitive SAR are 1p36, 4q13, and 9q34. Linkage of asthma to 1p36 in the Hutterites, 6 and linkage of elevated IgE levels, 18 and IgE specific to mites to 4p13.3 19 have been reported. Taken together with the findings of the present study, the data indicate that suggestive loci linked to SAR are common to asthma and SAR.…”

Section: Discussionmentioning

confidence: 97%

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Most cases are sporadic. However, there have been reports of autosomal dominant kindreds (36,(39)(40)(41)(42)(43)(44)(45) and autosomal recessive inheritance in consanguineous families (Renner et al submitted).…”

Section: Disorders Characterized By Excessive Ige Productionmentioning

confidence: 99%