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A STAT3 mutation in hyper-immunoglobulin E syndrome: A case report.

ABSTRACT: Hyper-immunoglobulin E syndrome (HIES) is a rare immunologic disorder. This syndrome is caused by mutations in signal transducer and activator of transcription 3 gene. The described case report showed clinical HIES features such as recurrent bacterial pneumonia, lung cysts, characteristic facial features and a newborn dermatitis. We found a clinical features score of 35 and a positive family history, which, together, made a HIES diagnosis very probable. During DNA analysis, a new, formerly unknown, 1067C?G (p.P356R) mutation, with reference sequence NM_139276.2, was found in the DNA binding site of the STAT3 gene. Both the child and his mother were affected. Thus, this family is affected by the autosomal dominant, HIES. This case report reveals a formerly unknown mutation, 1067C?G (p.P356R) in this gene.

SUBMITTER: Haenen F

PROVIDER: S-EPMC5020964 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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A STAT3 mutation in hyper-immunoglobulin E syndrome: A case report.

Haenen Filip F Alders Marielle M Dierckx Elke E Schil Paul Van PV Demeulemeester Veronique V Mortier Geert G Desager Kristine K

Journal of pediatric genetics 20130601 2

Hyper-immunoglobulin E syndrome (HIES) is a rare immunologic disorder. This syndrome is caused by mutations in signal transducer and activator of transcription 3 gene. The described case report showed clinical HIES features such as recurrent bacterial pneumonia, lung cysts, characteristic facial features and a newborn dermatitis. We found a clinical features score of 35 and a positive family history, which, together, made a HIES diagnosis very probable. During DNA analysis, a new, formerly unkno ...[more]

PMID: 27625845

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Hyper-IgE syndrome with STAT3 mutation: a case report in Mainland China.

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A deep intronic splice mutation of STAT3 underlies hyper IgE syndrome by negative dominance

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2020-04-30 | GSE149602 | GEO

Delayed diagnosis of hyperimmunoglobulin E syndrome with STAT3 mutation in mainland China: a case report and literature review.

Project description:Hyperimmunoglobulin E syndrome (HIES) is a rare immunologic disorder. Typical clinical features of HIES include recurrent bacterial pneumonia, lung cysts, characteristic facial features, and newborn dermatitis. The varied clinical presentation can lead to a delayed diagnosis. We herein present a sporadic case of HIES in a man who initially presented with a longstanding history of intractable skin abscesses.

| S-EPMC8755649 | biostudies-literature

A deep intronic splice mutation of <i>STAT3</i> underlies hyper IgE syndrome by negative dominance.

Project description:Heterozygous in-frame mutations in coding regions of human STAT3 underlie the only known autosomal dominant form of hyper IgE syndrome (AD HIES). About 5% of familial cases remain unexplained. The mutant proteins are loss-of-function and dominant-negative when tested following overproduction in recipient cells. However, the production of mutant proteins has not been detected and quantified in the cells of heterozygous patients. We report a deep intronic heterozygous STAT3 mutation, c.1282-89C>T, in 7 relatives with AD HIES. This mutation creates a new exon in the STAT3 complementary DNA, which, when overexpressed, generates a mutant STAT3 protein (D427ins17) that is loss-of-function and dominant-negative in terms of tyrosine phosphorylation, DNA binding, and transcriptional activity. In immortalized B cells from these patients, the D427ins17 protein was 2 kDa larger and 4-fold less abundant than wild-type STAT3, on mass spectrometry. The patients' primary B and T lymphocytes responded poorly to STAT3-dependent cytokines. These findings are reminiscent of the impaired responses of leukocytes from other patients with AD HIES due to typical STAT3 coding mutations, providing further evidence for the dominance of the mutant intronic allele. These findings highlight the importance of sequencing STAT3 introns in patients with HIES without candidate variants in coding regions and essential splice sites. They also show that AD HIES-causing STAT3 mutant alleles can be dominant-negative even if the encoded protein is produced in significantly smaller amounts than wild-type STAT3.

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Gastrointestinal Manifestations of STAT3-Deficient Hyper-IgE Syndrome.

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Project description:The Witkop syndrome is a rare autosomal dominant disorder characterized by the absence of several teeth and abnormalities of the nails. This is the first report of a rare genetic tooth and nail syndrome diagnosed in a 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia. A homozygous mutation was identified in 3'-UTR of MSX1 gene in the proband. The parents of the patient had no dental and nail anomalies.

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