ArticleJournal of clinical immunology2016
Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.
Article in Journal of clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 4 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 4 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Genetic Etiologies and Outcomes in Malignancy and Mortality in Activated Phosphoinositide 3-Kinase Delta Syndrome: A Systematic Review.Advances in therapy · 2025Pooled it
- Systematic review of mortality and survival rates for APDS.Clinical and experimental medicine · 2024Pooled it
- New classification and diagnostic criteria for insulin resistance syndrome.Diabetology international · 2022Guideline
- Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review.Clinical reviews in allergy & immunology · 2020Pooled it
- How I treat: Diagnostic clues and treatment for activated phosphoinositide 3-kinase delta syndrome.Journal of human immunity · 2026Review
- Hyperimmunoglobulin syndromes: A review of HIGM, HIES, and HIDS.Journal of translational autoimmunity · 2025Review
- A case of SHORT syndrome with a novel genetic mutation diagnosed 19 years after the onset of diabetes.Journal of diabetes investigation · 2025Article
- PIK3R1 mutations in individuals with insulin resistance or growth retardation: Case series and in silico functional analysis.Journal of diabetes investigation · 2025Article
- Overall survival among patients with activated phosphoinositide 3-kinase delta syndrome (APDS).Orphanet journal of rare diseases · 2025Article
- Article
- Paradoxical dominant negative activity of an immunodeficiency-associated activatingbioRxiv : the preprint server for biology · 2024Article
- Molecular assessment of splicing variants in a cohort of patients with inborn errors of immunity: methodological approach and interpretation remarks.Frontiers in immunology · 2024Article
- Hyperactivation of the PI3K pathway in inborn errors of immunity: current understanding and therapeutic perspectives.Immunotherapy advances · 2024Review
- Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2.The Journal of experimental medicine · 2023Article
- SHORT Syndrome: an Update on Pathogenesis and Clinical Spectrum.Current diabetes reports · 2022Review
- Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Review
- PI3K Isoforms in B Cells.Current topics in microbiology and immunology · 2022Article
- Insulin resistance and exaggerated insulin sensitivity triggered by single-gene mutations in the insulin signaling pathway.Diabetology international · 2021Article
- A novel PIK3R1 mutation of SHORT syndrome in a Chinese female with diffuse thyroid disease: a case report and review of literature.BMC medical genetics · 2020Article
- APDS2 and SHORT Syndrome in a Teenager with PIK3R1 Pathogenic Variant.Journal of clinical immunology · 2020Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation's effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient's EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435-474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome.
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