Hyper IgE syndrome associated with novel and recurrent STAT3 mutations

Deng, Ying; Li, Tong; Xie, Xiaoqin; Xia, Dengmei; Ding, Li; Xiang, Hongmei; Jessie, J; Li, Wei

doi:10.1097/md.0000000000014003

Cited by 13 publications

(16 citation statements)

References 14 publications

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“…Notably, one patients' variant is derived from his father, who has de nove mutation in STAT3 and clinical symptom has appeared when he was young. In keeping with numerous reports [21][22][23] that c. 1144C > T (R382W) is a hotspot mutation in patients carrying STAT3 gene mutation in China. On the other hand, different from that literature, secondary common mutation c.…”

Section: Discussionsupporting

confidence: 87%

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The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutation

Wang

Sun

Liu

et al. 2020

Preprint

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Background: Loss-of-function (LOF) mutation in signal transducer and activator of transcription 3 (STAT3) was one of the causes of the hyper immunoglobulin E (IgE) syndrome (HIES), while gain-of-function mutation (GOF) in STAT3 leads to immune dysregulation diseases. We retrospectively report 11 LOF STAT3 patients and 1 GOF STAT3 patient and illustrate their onset age, common clinical symptoms, immunologic and molecular manifestation. Methods: 12 patients were enrolled in our study. Serum immunoglobulins, lymphocyte subset detection and whole-exome sequencing were performed. Results: The median onset age of STAT3-deficient patients was 1.89 years. Eczema, recurrent respiratory infection, apparent fever, abscesses and Staphylococcus aureus infection was the classical manifestation. Elevated serum IgE level is not entirely unanimous with high eosinophils counts. Moderate viral DNA was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common spot, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients obtained a notable improvement after received intravenous immunoglobulin (IVIG). Conclusion: We believe IVIG may help reduce the opportunity of infection in STAT3-deficient patients. Significant variance at onset age probably is a great challenge for clinicians and urgently needs early diagnosis and treatment.

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Section: Discussionsupporting

confidence: 87%

“…Different from two large-scale STAT3-deficient cohort studies in China [21][22][23], a few patients emerge classical non-immunological features, including special faces, dental and developmental abnormality.…”

Section: Discussionmentioning

confidence: 83%

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutation

Wang

Sun

Liu

et al. 2020

Preprint

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“…Currently, there is no national PID registry in China, meaning no accurate prevalence data on AD‐HIES. Up to this date, a total of 40 Chinese AD‐HIES patients with STAT3 deficiency have been reported in English and Chinese literature (including seven patients our group previously reported and two patients from Taiwan) 15–18 . Combining these 13 new cases with the 40 cases reported in the literature gives a total number of AD‐HIES cases to 53 in China.…”

Section: Discussionmentioning

confidence: 97%

Autosomal dominant hyper IgE syndrome from a single centre in Chongqing, China (2009‐2018)

et al. 2020

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Autosomal dominant hyper IgE syndrome (AD-HIES) caused by STAT3 gene mutation is a rare primary immunodeficiency disease. To better understand the disease, we described the clinical characteristics of 20 AD-HIES patients in Chongqing, China and explored the effect of mutations in different domains of STAT3 gene on the function of STAT3 protein by Western blot and confocal microscopy. The mean age at onset was 0.12 years. The mean age at diagnosis was 5.31 years. The most common presentation was eczema, pneumonia, skin abscesses and chronic mucocutaneous candidiasis. Seven patients suffered from BCG complications. R382W/Q were identified in 12 patients, V637M mutation in three patients. Three patients have died. The phosphorylated STAT3 was expressed more in wild-type(WT) and R382W mutant STAT3 in the cytoplasm of COS7 cells with epidermal growth factor(EGF) stimulation, less in the V637M mutation and T620S mutation. Dynamic observation showed that STAT3 cytoplasmic accumulation and nuclear translocation occurred rapidly after EGF stimulation in WT-STAT3-GFP, the time of accumulation and nuclear translocation was later and the expression was less in R382W-STAT3-GFP compared with WT-STAT3-GFP, followed by V637M and T620S mutation. These results suggested that our patients had earlier onset, diagnostic age and higher rate of BCG complications. However, our patients had higher incidence of mortality though the earlier diagnostic age. We did not find a significant genotype/phenotype correlation, but Src homology 2 domain mutations (V637M and T620S) had a greater effect on STAT3 phosphorylation and nuclear translocation than DNA-binding domain mutation (R382W) in vitro.

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“…Congenital defects, such as atrial septal defects, laryngeal clefts and cryptorchidism, occurred to different degrees. In contrast to two large-scale STAT3-de cient cohort studies in China [11,12,23], few patients had the classic nonimmunological features, including particular facial features and dental and developmental abnormalities. This was a retrospective analysis; doctors are likely to overlook some slight facial changes, and many patients were young when they rst visited our hospital.…”

Section: Discussionmentioning

confidence: 60%

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

Lin

Wang

Sun

et al. 2020

Preprint

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Background: Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.Methods: Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.Results: The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. Conclusion: We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.

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Hyper IgE syndrome associated with novel and recurrent STAT3 mutations

Cited by 13 publications

References 14 publications

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutation

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutation

Autosomal dominant hyper IgE syndrome from a single centre in Chongqing, China (2009‐2018)

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

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