ArticleAmerican journal of human genetics2013
Mutations in PIK3R1 cause SHORT syndrome.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 3 of them syntheses that pooled it.
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102 citing papers in PubMed, 3 syntheses or guidelines pooled it, 196 citations in OpenAlex.
- New classification and diagnostic criteria for insulin resistance syndrome.Diabetology international · 2022Guideline
- Multitrait genome association analysis identifies new susceptibility genes for human anthropometric variation in the GCAT cohort.Journal of medical genetics · 2018Pooled it
- Clinical Features and Management of Non-HIV-Related Lipodystrophy in Children: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2017Pooled it
- How I treat: Diagnostic clues and treatment for activated phosphoinositide 3-kinase delta syndrome.Journal of human immunity · 2026Review
- Lipodystrophy: an uncommon cause of insulin resistance and young-onset diabetes.JCEM case reports · 2026Article
- Population-scale gene-based analysis of whole-genome sequencing provides insights into metabolic health.Nature genetics · 2025Article
- Article
- Management of pregnancy with metformin: Case reports for genetic insulin resistance syndrome and a literature review for gestational and type 2 diabetes.Journal of diabetes investigation · 2025Review
- PIK3R1 mutations in individuals with insulin resistance or growth retardation: Case series and in silico functional analysis.Journal of diabetes investigation · 2025Article
- A case of SHORT syndrome with a novel genetic mutation diagnosed 19 years after the onset of diabetes.Journal of diabetes investigation · 2025Article
- The metabolically protective energy expenditure increase ofAmerican journal of physiology. Endocrinology and metabolism · 2025Article
- KBTBD2 controls bone development by regulating IGF-1 signaling during osteoblast differentiation.Cell death and differentiation · 2025Article
- Article
- Mechanisms and therapeutics of insulin signaling transduction genes in diabetic cardiomyopathy: a comprehensive updated review.Frontiers in endocrinology · 2025Review
- Diabetes mellitus in SHORT syndrome managed with multi-agent oral therapies: a case report and literature review.Therapeutic advances in endocrinology and metabolism · 2025Article
- Paradoxical dominant negative activity of an immunodeficiency-associated activatingbioRxiv : the preprint server for biology · 2024Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- A Novel Variant of the PIK3R1 Gene Mutation Associated With SHORT Syndrome and Agammaglobulinemia.Cureus · 2024Article
- TargetingHeliyon · 2024Article
- Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3Nature structural & molecular biology · 2024Article
42 more citing papers are in PubMed but not listed here.
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20 authors at 12 institutions in 5 countries.
Funding
Abstract
SHORT syndrome is a rare, multisystem disease characterized by short stature, anterior-chamber eye anomalies, characteristic facial features, lipodystrophy, hernias, hyperextensibility, and delayed dentition. As part of the FORGE (Finding of Rare Disease Genes) Canada Consortium, we studied individuals with clinical features of SHORT syndrome to identify the genetic etiology of this rare disease. Whole-exome sequencing in a family trio of an affected child and unaffected parents identified a de novo frameshift insertion, c.1906_1907insC (p.Asn636Thrfs*18), in exon 14 of PIK3R1. Heterozygous mutations in exon 14 of PIK3R1 were subsequently identified by Sanger sequencing in three additional affected individuals and two affected family members. One of these mutations, c.1945C>T (p.Arg649Trp), was confirmed to be a de novo mutation in one affected individual and was also identified and shown to segregate with the phenotype in an unrelated family. The other mutation, a de novo truncating mutation (c.1971T>G [p.Tyr657*]), was identified in another affected individual. PIK3R1 is involved in the phosphatidylinositol 3 kinase (PI3K) signaling cascade and, as such, plays an important role in cell growth, proliferation, and survival. Functional studies on lymphoblastoid cells with the PIK3R1 c.1906_1907insC mutation showed decreased phosphorylation of the downstream S6 target of the PI3K-AKT-mTOR pathway. Our findings show that PIK3R1 mutations are the major cause of SHORT syndrome and suggest that the molecular mechanism of disease might involve downregulation of the PI3K-AKT-mTOR pathway.
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