ArticleAmerican journal of human genetics2013
PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy.
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 107 papers, 1 of them a synthesis that pooled it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it.
- New classification and diagnostic criteria for insulin resistance syndrome.Diabetology international · 2022Guideline
- How I treat: Diagnostic clues and treatment for activated phosphoinositide 3-kinase delta syndrome.Journal of human immunity · 2026Review
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Metreleptin In SHORT Syndrome With Uncontrolled Diabetes.JCEM case reports · 2025Article
- Population-scale gene-based analysis of whole-genome sequencing provides insights into metabolic health.Nature genetics · 2025Article
- Identification of A Novel Mutation of SHORT Syndrome: A Case Report.Clinical case reports · 2025Article
- 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
- KBTBD2 controls bone development by regulating IGF-1 signaling during osteoblast differentiation.Cell death and differentiation · 2025Article
- The metabolically protective energy expenditure increase ofAmerican journal of physiology. Endocrinology and metabolism · 2025Article
- Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders.Journal of inherited metabolic disease · 2025Review
- Article
- 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
- Small RNAs and tooth development: The role of microRNAs in tooth agenesis and impaction.Journal of dental sciences · 2024Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Role ofArchives of Razi Institute · 2024Article
- Structural and Dynamic Analyses of Pathogenic Variants inLife (Basel, Switzerland) · 2024Article
47 more citing papers are in PubMed but not listed here.
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28 authors.
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Abstract
Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts.
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