ArticleEMBO molecular medicine2016
Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood.Endocrine reviews · 2023Guideline
- Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS.The Journal of clinical endocrinology and metabolism · 2021Trial
- Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density.The Journal of clinical endocrinology and metabolism · 2017Trial
- Stanniocalcin-1 and -2: The insulin-like growth factor system and beyond.Molecular biology reports · 2026Review
- Idiopathic short stature in the genomic era: a focused narrative review of genotype-phenotype correlation, selective neuroimaging, IGF-1 biology, and growth hormone responsiveness.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026Review
- Sex-specific hormonal rescue of bone growth in PAPPA2-deficient mice : a role for cannabinoid receptors and STAT3.Bone & joint research · 2026Article
- The Critical Functions of FGF2, LIF and IGF1 in the Improvement of In Vitro Embryo Production.Biomolecules · 2026Review
- Article
- Biomarkers in the Newborn with Fetal Growth Retardation and Early Impairment of Heart Function.Hormone research in paediatrics · 2025Article
- Diagnostic Challenges of Short Stature and Growth Hormone Insufficiency Across Different Genetic Etiologies.Biomedicines · 2025Review
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Cadherin-16 regulates acoustic sensory gating in zebrafish through endocrine signaling.PLoS biology · 2025Article
- The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System.Genome biology and evolution · 2025Article
- Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.Nature communications · 2025Article
- Cadherin 16 promotes sensory gating via the endocrine corpuscles of Stannius.bioRxiv : the preprint server for biology · 2024Article
- The metalloproteinase PAPP-A is required for IGF-dependent chondrocyte differentiation and organization.Scientific reports · 2024Article
- Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis.Endocrinology · 2024Review
- Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments.Biology of sex differences · 2024Article
- Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.medRxiv : the preprint server for health sciences · 2024Article
- Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population.Scientific reports · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 15 institutions in 4 countries.
Funding
Abstract
Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.
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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.