Evidence map›Paper›PMID 26047794›Full record

ArticleJournal of the American Society of Nephrology : JASN2016

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

Karl P Schlingmann, Justyna Ruminska, Martin Kaufmann, Ismail Dursun, Monica Patti, Birgitta Kranz, Ewa Pronicka, Elzbieta Ciara, Teoman Akcay, Derya Bulus and 18 more

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In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 2 pooled it
15.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

136 citing papers in PubMed, 2 syntheses or guidelines pooled it, 276 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Article
  4. Article
  5. Nucleic Acids as Emerging Regulators of Calcium Phosphate Biomineralization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Fifty Shades of Risk: Population Studies and the Genetic Architecture of Kidney Diseases.Journal of the American Society of Nephrology : JASN · 2026
    Review
  16. Article
  17. Article
  18. Diagnosis and Management of Hypophosphatemic Disorders.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2025
    Review
  19. Genetic and Clinical Characterization of a Large Cohort with Suspected Monogenic Stone Disease.Clinical journal of the American Society of Nephrology : CJASN · 2025
    Article
  20. Review

76 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 18 institutions in 11 countries.

Karl P SchlingmannDepartment of General Pediatrics, University Children's Hospital, Münster, Germany;
Justyna RuminskaInstitute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland;
Martin KaufmannDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada;
Ismail DursunDepartment of General Pediatrics, University Children's Hospital, Münster, Germany; Department of Pediatrics, Kayseri University, Kayseri, Turkey;
Monica PattiInstitute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland;
Birgitta KranzDepartment of General Pediatrics, University Children's Hospital, Münster, Germany;
Ewa PronickaDepartment of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland;
Elzbieta CiaraDepartment of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland;
Teoman AkcayDepartment of Pediatrics, Division of Pediatric Endocrinology, Marmara University, Istanbul, Turkey;
Derya BulusDepartment of Pediatric Endocrinology, Keçiören Research and Educational Hospital, Ankara, Turkey;
Elisabeth A M CornelissenPediatric Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
Aneta GawlikDepartment of Pediatrics, Medical University of Silesia, Katowice, Poland;
Przemysław SikoraDepartment of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland;
Ludwig PatzerChildren's Hospital St. Elisabeth and St. Barbara, Halle/Saale, Germany;
Matthias GalianoDepartment of Pediatrics, Friedrich-Alexander-University, Erlangen, Germany;
Veselin BoyadzhievDepartment of Pediatrics, University Hospital St. Marina, Varna Medical University, Varna, Bulgaria;
Miroslav DumicDepartment of Pediatrics, University Hospital Center, Zagreb, Croatia;
Asaf VivanteSheba Medical Center, Tel Aviv, Israel;
Robert KletaUniversity College London, London, United Kingdom;
Benjamin DekelSheba Medical Center, Tel Aviv, Israel;
Elena LevtchenkoDepartment of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium;
René J BindelsDepartment of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands; and.
Stephan RustDepartment of General Pediatrics, University Children's Hospital, Münster, Germany;
Ian C ForsterInstitute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland;
Nati HernandoInstitute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland;
Glenville JonesDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Carsten A WagnerInstitute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland;
Martin KonradDepartment of General Pediatrics, University Children's Hospital, Münster, Germany; konradma@uni-muenster.de.
University of Zurich · CHUniversity Hospital Münster · DEChildren's Memorial Health Institute · PLSheba Medical Center · ILFriedrich-Alexander-Universität Erlangen-Nürnberg · DEKayseri ÜniversitesiKrankenhaus St. Elisabeth und St. Barbara · DEKU Leuven · BEMarmara University · TRMedical University of Lublin · PLMedical University of Silesia · PLQueen's University · CARadboud University Medical Center · NLRadboud University Nijmegen · NLS.B. Keçiören Eğitim ve Araştırma Hastanesi · TRUniversity College London · GBUniversity Hospital Centre Zagreb · HRUniversity Hospital St. Marina · BG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH.

Indexed as

MutationAnimalsGenes, RecessiveHumansHypercalcemiaInfantInfant, NewbornInfant, Newborn, DiseasesMetabolism, Inborn ErrorsMiceMice, KnockoutSodium-Phosphate Cotransporter ProteinsSodium-Phosphate Cotransporter Proteins, Type IIaSLC34A1 protein, humanSlc34a1 protein, mouseSodium-Phosphate Cotransporter ProteinsSodium-Phosphate Cotransporter Proteins, Type IIaactivated Vitamin Dgenetic renal diseasehypercalciuriamineral metabolismmolecular genetics

Identifiers

PMID26047794
PMCPMC4731111
OpenAlexW2209323210

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.