ArticleThe Journal of clinical investigation2003
Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 296 citations in OpenAlex.
- Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population.PloS one · 2013Pooled it
- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Effectiveness and Safety of Setmelanotide in a Patient With a Heterozygous PCSK1 Deficiency.Obesity (Silver Spring, Md.) · 2026Article
- Review
- Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes.bioRxiv : the preprint server for biology · 2025Article
- The Interplay of UCP3 and PCSK1 Variants in Severe Obesity.Current obesity reports · 2025Review
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Congenital Diarrhoeas and Enteropathies.Nutrients · 2024Review
- Differentiating monogenic and syndromic obesities from polygenic obesity: Assessment, diagnosis, and management.Obesity pillars · 2024Review
- Arcuate Nucleus of the Hypothalamus: Anatomy, Physiology, and Diseases.Experimental neurobiology · 2023Review
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis.Nature cell biology · 2023Article
- The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits.Nature reviews. Endocrinology · 2022Review
- Rare HeterozygousGenes · 2022Review
- Proteins and proteases of Prader-Willi syndrome: a comprehensive review and perspectives.Bioscience reports · 2022Review
- The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.Endocrinology · 2022Article
- Genetic causes of neonatal and infantile hypercalcaemia.Pediatric nephrology (Berlin, Germany) · 2022Review
- Modulation of PC1/3 activity by a rare double-site homozygous mutation.Frontiers in pediatrics · 2022Article
- Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.Endocrinology · 2021Review
- Gene expression atlas of energy balance brain regions.JCI insight · 2021Article
52 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 15 institutions in 5 countries.
Funding
Abstract
We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A's negligible PC1 activity, some mature ACTH and glucagon-like peptide 17-36(amide) were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species.
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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.