Destructive pulmonary staphylococcal infection in a boy with hyper-IgE syndrome: a novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene (p.Y657S)

Liu, Jinyan; Li, Qiang; Chen, Tingting; Guo, Xia; Ge, Jiao; Yuan, Li-Xing

doi:10.1007/s00431-010-1349-6

Cited by 13 publications

(16 citation statements)

References 20 publications

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“…In HIES patients of Chinese descent, four with de novo heterozygous STAT3 mutations -two with R382W and Q469R in Taiwan and another two with H437P and Y657S in mainland China (Liu et al 2010;Xie et al 2010) -and the first homozygous DOCK8 deletion in one siblings were identified. Four patients with higher severity scores of the AD-HIES phenotype and three with the AR-HIES phenotype have the wild type STAT3, TYK2 and DOCK8.…”

Section: Discussionmentioning

confidence: 98%

Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES)

Lee¹,

Huang²,

Lin³

et al. 2011

Immunobiology

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Section: Discussionmentioning

confidence: 98%

Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES)

Lee¹,

Huang²,

Lin³

et al. 2011

Immunobiology

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“…Underlined mutations were identified in patients from the current study; mutations not underlined were identified in previous studies. [2–4,28,29,33,35,36,41,47,52,55,60-62,70,71] The positions of all known mutations are indicated in amino acid nomenclature, with the exception of mutations starting with c. at the bottom, which are shown in nucleotide nomenclature.…”

Section: Figurementioning

confidence: 99%

“…Since 2007, up to 230 STAT3-deficient patients have been reported in individual case reports [2–4,13, 33, 35, 41, 43, 44, 55, 61, 68, 71] or national or international series, including 8 patients (Japan), [47] 37 (United States and Europe), [60] 12 (Lebanon and Europe), [29] 50 (international), [28] 64 (international), [70] and 48 patients (international). [62] However, most reports have focused on the molecular and cellular defects of the patients, providing little clinical information.…”

Section: Introductionmentioning

confidence: 99%

Autosomal Dominant STAT3 Deficiency and Hyper-IgE Syndrome

Chandesris¹,

Melki²,

Natividad³

et al. 2012

Medicine

286

160

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Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented.

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“…In 2007, signal transducer and activator of transcription 3 (STAT3) mutations were found to be the cause of the sporadic and autosomal dominant hyper‐IgE syndrome (AD‐HIES) , and patients showed extremely low or absent T helper 17 cells (Th17) in their peripheral blood . Few Chinese cases of HIES due to STAT3 mutations were reported in Hong Kong, Taiwan and mainland China ; no investigations have analysed Th17 cell numbers in patients with HIES in mainland China. In this study, we described the phenotypes of Chinese children with HIES, carried out STAT3 gene sequencing in all nine patients and quantified Th17 cell numbers in seven patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical Features, STAT3 Gene Mutations and Th17 Cell Analysis in Nine Children with Hyper‐IgE Syndrome in Mainland China

et al. 2013

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Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency disease characterized by eczema, recurrent staphylococcal aureus skin abscesses, pneumonia with pneumatocele formation, remarkably high serum IgE levels, eosinophilia and involvement of skeleton and connective tissues. Heterozygous signal transducer and activator of transcription 3 (STAT3) mutations were shown to be the cause of autosomal dominant HIES (AD-HIES). In this study, we diagnosed nine patients with HIES from 9 unrelated families on the basis of a National Institutes of Health (NIH) score of ≥40 points, sequenced the STAT3 gene of all nine patients, and quantified Th17 cells in peripheral blood of seven patients by flow cytometry in mainland China. All nine patients had characteristic manifestation of HIES with the range of NIH scores 45-77 points. STAT3 hot mutations V637M or R382W/Q were identified in five patients. We identified two novel heterozygous missense mutations (T620S and R609G) located in Src homology 2 (SH2) domain in two patients, respectively. In two other patients, no STAT3 mutations were found. Quantified Th17 cell numbers were markedly decreased or absent (0-0.28% of CD4 + T cells) in six patients with STAT3 mutations and almost normal (0.53% of CD4 + T cells) in one wild-type STAT3 patient compared with healthy controls (0.40-2.25% of CD4 + T cells). These results suggest that not all patients with HIES who had NIH scores over 40 points carry STAT3 mutations, those whose Th17 cell numbers strikingly decreased probably had AD-HIES with STAT3 mutations.

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Destructive pulmonary staphylococcal infection in a boy with hyper-IgE syndrome: a novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene (p.Y657S)

Abstract: The mutation,p.Y657S,in SH2 domain of STAT3 is a disease-causing mutation in the boy with HIES.

Cited by 13 publications

References 20 publications

Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES)

Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES)

Autosomal Dominant STAT3 Deficiency and Hyper-IgE Syndrome

Clinical Features, STAT3 Gene Mutations and Th17 Cell Analysis in Nine Children with Hyper‐IgE Syndrome in Mainland China

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