ArticleDiabetes2016
Targeted Deep Sequencing in Multiple-Affected Sibships of European Ancestry Identifies Rare Deleterious Variants in PTPN22 That Confer Risk for Type 1 Diabetes.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Manipulation of Alternative Splicing ofCells · 2026Article
- Lessons and Applications of Omics Research in Diabetes Epidemiology.Current diabetes reports · 2024Review
- Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions.International journal of obesity (2005) · 2023Review
- Shifts in isoform usage underlie transcriptional differences in regulatory T cells in type 1 diabetes.Communications biology · 2023Article
- Impacts of SARS-CoV-2 on diabetes mellitus: A pre and post pandemic evaluation.World journal of virology · 2023Review
- Genetics of diabetes.World journal of diabetes · 2023Review
- UBASH3A Interacts with PTPN22 to RegulateInternational journal of molecular sciences · 2023Article
- The missing heritability in type 1 diabetes.Diabetes, obesity & metabolism · 2022Review
- Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction.International journal of molecular sciences · 2022Review
- Environmental Triggering of Type 1 Diabetes Autoimmunity.Frontiers in endocrinology · 2022Review
- Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course.Journal of the Endocrine Society · 2021Article
- Emerging roles of rare and low-frequency genetic variants in type 1 diabetes mellitus.Journal of medical genetics · 2021Review
- Influence ofFrontiers in immunology · 2021Review
- Search for Genetic Predictors of Adult Autoimmune Polyendocrine Syndrome in Monozygotic Twins.Clinical medicine insights. Endocrinology and diabetes · 2021Article
- Regulation of inflammation in diabetes: From genetics to epigenomics evidence.Molecular metabolism · 2020Review
- Genetics of diabetes mellitus and diabetes complications.Nature reviews. Nephrology · 2020Review
- UBASH3A Regulates the Synthesis and Dynamics of TCR-CD3 Complexes.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Disease-specific biases in alternative splicing and tissue-specific dysregulation revealed by multitissue profiling of lymphocyte gene expression in type 1 diabetes.Genome research · 2017Article
- Primer in Genetics and Genomics, Article 5-Further Defining the Concepts of Genotype and Phenotype and Exploring Genotype-Phenotype Associations.Biological research for nursing · 2017Article
- UBASH3A Mediates Risk for Type 1 Diabetes Through Inhibition of T-Cell Receptor-Induced NF-κB Signaling.Diabetes · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Despite finding more than 40 risk loci for type 1 diabetes (T1D), the causative variants and genes remain largely unknown. Here, we sought to identify rare deleterious variants of moderate-to-large effects contributing to T1D. We deeply sequenced 301 protein-coding genes located in 49 previously reported T1D risk loci in 70 T1D cases of European ancestry. These cases were selected from putatively high-risk families that had three or more siblings diagnosed with T1D at early ages. A cluster of rare deleterious variants in PTPN22 was identified, including two novel frameshift mutations (ss538819444 and rs371865329) and two missense variants (rs74163663 and rs56048322). Genotyping in 3,609 T1D families showed that rs56048322 was significantly associated with T1D and that this association was independent of the T1D-associated common variant rs2476601. The risk allele at rs56048322 affects splicing of PTPN22, resulting in the production of two alternative PTPN22 transcripts and a novel isoform of LYP (the protein encoded by PTPN22). This isoform competes with the wild-type LYP for binding to CSK and results in hyporesponsiveness of CD4(+) T cells to antigen stimulation in T1D subjects. These findings demonstrate that in addition to common variants, rare deleterious variants in PTPN22 exist and can affect T1D risk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.