Evidence map›Paper›PMID 27380894›Full record

ArticleNature communications2016

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta.

Uschi Lindert, Wayne A Cabral, Surasawadee Ausavarat, Siraprapa Tongkobpetch, Katja Ludin, Aileen M Barnes, Patra Yeetong, Maryann Weis, Birgit Krabichler, Chalurmpon Srichomthong and 11 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04115774 (Registry of Osteogenesis Imperfecta That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Quality of Life Data. Data is Linked to Patients Biological Samples, When Available), which is not on this map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
18.3field-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.

NCT04115774 recruitingnot on this map

Registry of Osteogenesis Imperfecta That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Quality of Life Data. Data is Linked to Patients Biological Samples, When Available

Typeobservational_patient_registrySponsorLuca SangiorgiRan2013 to 2032Enrolled5,000ConditionsOsteogenesis ImperfectaArmsbisphosphonates
3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 143 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Osteogenesis imperfecta: pathogenesis, classification, and treatment.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025
    Review
  11. Review
  12. Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024
    Review
  13. Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.Genetics in medicine : official journal of the American College of Medical Genetics · 2024
    Article
  14. Article
  15. Review
  16. Current Status of Next-Generation Sequencing in Bone Genetic Diseases.International journal of molecular sciences · 2023
    Review
  17. Review
  18. Review
  19. Review
  20. Review

14 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

21 authors at 7 institutions in 8 countries.

Uschi LindertDivision of Metabolism, Connective Tissue Unit and Children's Research Center, University Children's Hospital Zurich, Zurich 8032, Switzerland.
Wayne A CabralSection on Heritable Disorders of Bone and Extracellular Matrix, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Surasawadee AusavaratCenter of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Siraprapa TongkobpetchCenter of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Katja LudinCenter for Laboratory Medicine, Department of Medical Genetics, Kantonsspital Aarau, Aarau 5001, Switzerland.
Aileen M BarnesSection on Heritable Disorders of Bone and Extracellular Matrix, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Patra YeetongCenter of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Maryann WeisDepartment of Orthopedics and Sports Medicine, University of Washington, Seattle, Washington 98195, USA.
Birgit KrabichlerDivision of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria.
Chalurmpon SrichomthongCenter of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Elena N MakareevaSection on Physical Biochemistry, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Andreas R JaneckeDivision of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria.ORCID http://orcid.org/0000-0001-7155-0315
Sergey LeikinSection on Physical Biochemistry, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Benno RöthlisbergerCenter for Laboratory Medicine, Department of Medical Genetics, Kantonsspital Aarau, Aarau 5001, Switzerland.
Marianne RohrbachDivision of Metabolism, Connective Tissue Unit and Children's Research Center, University Children's Hospital Zurich, Zurich 8032, Switzerland.
Ingo KennerknechtInstitute of Human Genetics, Westfälische Wilhelms University, Münster 48149, Germany.
David R EyreDepartment of Orthopedics and Sports Medicine, University of Washington, Seattle, Washington 98195, USA.
Kanya SuphapeetipornCenter of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Cecilia GiuntaDivision of Metabolism, Connective Tissue Unit and Children's Research Center, University Children's Hospital Zurich, Zurich 8032, Switzerland.
Joan C MariniSection on Heritable Disorders of Bone and Extracellular Matrix, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Vorasuk ShotelersukCenter of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.ORCID http://orcid.org/0000-0002-1856-0589
Thai Red Cross Society · THNational Institutes of Health · USUniversity Children's Hospital Zurich · CHInnsbruck Medical University · ATKantonsspital Aarau · CHUniversity of Washington · USUniversity of Münster · DE

Funding

Collagen-related diseases ZIAHD000256 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LEIKIN, SERGEY · 2009 to 2025
$19.7M
Heritable Disorders Of Connective TissueZIAHD000408 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MARINI, JOAN C · 2009 to 2023
$13.4M
Project 3: Collagen post-translational modification and cross-linking in OIP01HD070394 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI LEE, BRENDAN · 2011 to 2020
$13.4M
Collagen Cross-linking in Skeletal Aging and DiseaseR37AR037318 · NIAMS · UNIVERSITY OF WASHINGTON · PI EYRE, DAVID R · 2010 to 2019
$3.4M
PATHOLOGY OF INBORN SKELETAL DISEASESR01AR037318 · NIAMS · UNIVERSITY OF WASHINGTON · PI EYRE, DAVID R · 1986 to 2009
$3.4M
Collagens of Cartilage and the Intervertebral DiscR01AR036794 · NIAMS · UNIVERSITY OF WASHINGTON · PI EYRE, DAVID R · 1986 to 2014
$3.3M
NIAMS NIH HHS R01 AR036794NIAMS NIH HHS R01 AR037318NIAMS NIH HHS R37 AR037318NICHD NIH HHS P01 HD070394
6 · The paper itself

Abstract

Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development.

Indexed as

Mutation, MissenseActivating Transcription Factor 6AdultAgedCell DifferentiationCell MembraneCollagen Type ICyclic AMP Response Element-Binding ProteinGene Expression RegulationGenes, RecessiveHumansHydroxylationMaleMetalloendopeptidasesMiddle AgedNerve Tissue ProteinsActivating Transcription Factor 6ATF6 protein, humanCollagen Type ICREB3L1 protein, humanCyclic AMP Response Element-Binding Proteinlysyl hydroxylase 1, humanMBTPS2 protein, humanMetalloendopeptidasesNerve Tissue ProteinsProcollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseSterol Regulatory Element Binding Proteins

Identifiers

PMID27380894
PMCPMC4935805
OpenAlexW2465597841

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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.