ArticleGastroenterology2013
Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.Human molecular genetics · 2015Pooled it
- A domain-swapped proPC1/3 structure reveals a conformational checkpoint for ER export.bioRxiv : the preprint server for biology · 2026Article
- Rare Presentation of Heterozygous PCSK1 Deficiency in an Adolescent Male.Case reports in pediatrics · 2026Article
- Pathogenic Deep Intronic PCSK1 Variant Causes Proprotein Convertase 1/3 Deficiency in a Family.Clinical genetics · 2025Article
- Central Adrenal Insufficiency: Etiology and Diagnostic ApproachJournal of clinical research in pediatric endocrinology · 2025Review
- Differentiating monogenic and syndromic obesities from polygenic obesity: Assessment, diagnosis, and management.Obesity pillars · 2024Review
- Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.The American journal of clinical nutrition · 2024Review
- Appetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity.Endocrine reviews · 2024Review
- Review
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.Human molecular genetics · 2023Article
- Rare HeterozygousGenes · 2022Review
- Prohormone convertase 1/3 deficiency causes obesity due to impaired proinsulin processing.Nature communications · 2022Article
- The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.Endocrinology · 2022Article
- Characterization of the genetic architecture of infant and early childhood body mass index.Nature metabolism · 2022Article
- Modulation of PC1/3 activity by a rare double-site homozygous mutation.Frontiers in pediatrics · 2022Article
- Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages.Cancer gene therapy · 2022Article
- Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.Endocrinology · 2021Review
- Advances in differential diagnosis and management of growth hormone deficiency in children.Nature reviews. Endocrinology · 2021Review
- Gene expression atlas of energy balance brain regions.JCI insight · 2021Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 13 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsProprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency.
methodsWe studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins.
resultsWe identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears.
conclusionsIn a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption.
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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.