ArticleNature genetics2014
Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.
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170 citing papers in PubMed, 1 synthesis or guideline pooled it, 315 citations in OpenAlex.
- Mapping the Diverse Genetic Disorders and Rare Diseases Among the Syrian Population: Implications on Refugee Health and Health Services in Host Countries.Journal of immigrant and minority health · 2020Pooled it
- Dorsal Pancreatic Agenesis Associated With New-Onset Diabetes Mellitus and Acute Pancreatitis in an 18-Year-Old Man: A Case Report.Clinical case reports · 2026Article
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- Systematic reanalysis of next-generation sequencing data in 101 neuromuscular disorder families enhances diagnostic yield, reveals intronic variants, and identifies a novel disease gene.Journal of neurology · 2026Article
- Transcriptomic regulation of pancreatic acinar cell homeostasis and plasticity.Biochemical Society transactions · 2026Review
- Functional genomics analysis of developing zebrafish and human endoderm reveals highly conservedGenome research · 2026Article
- Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes.American journal of human genetics · 2026Article
- Whole Genome Sequencing of Discordant Monozygotic Twins Reveals Regulatory Variants Associated With Nonsyndromic Orofacial Clefts.Human mutation · 2026Article
- Global perspectives on monogenic forms of diabetes.Diabetologia · 2025Review
- Enhancing the diagnostic yield of monogenic diabetes in unresolved cases with early-onset hyperglycemia.Communications medicine · 2025Article
- Neonatal and Syndromic Forms of Diabetes.Current diabetes reports · 2025Review
- Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity.Genome medicine · 2025Article
- Whole-genome sequencing analysis identifies rare, large-effect noncoding variants and regulatory regions associated with circulating protein levels.Nature genetics · 2025Article
- Review
- A RareInternational journal of endocrinology and metabolism · 2025Article
- Structural framework to address variant-gene relationship in primary open-angle glaucoma.Vision research · 2025Review
- Noncoding variation near UBE2E2 orchestrates cardiometabolic pathophenotypes through polygenic effectors.JCI insight · 2024Article
- Genetic variant profiling of neonatal diabetes mellitus in Iranian patients: Unveiling 58 distinct variants in 14 genes.Journal of diabetes investigation · 2024Article
- A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.Nature communications · 2024Article
- CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant.Cell reports · 2024Article
110 more citing papers are in PubMed but not listed here.
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21 authors at 5 institutions in 2 countries.
Funding
Abstract
The contribution of cis-regulatory mutations to human disease remains poorly understood. Whole-genome sequencing can identify all noncoding variants, yet the discrimination of causal regulatory mutations represents a formidable challenge. We used epigenomic annotation in human embryonic stem cell (hESC)-derived pancreatic progenitor cells to guide the interpretation of whole-genome sequences from individuals with isolated pancreatic agenesis. This analysis uncovered six different recessive mutations in a previously uncharacterized ~400-bp sequence located 25 kb downstream of PTF1A (encoding pancreas-specific transcription factor 1a) in ten families with pancreatic agenesis. We show that this region acts as a developmental enhancer of PTF1A and that the mutations abolish enhancer activity. These mutations are the most common cause of isolated pancreatic agenesis. Integrating genome sequencing and epigenomic annotation in a disease-relevant cell type can thus uncover new noncoding elements underlying human development and disease.
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