Evidence map›Paper›PMID 26479409›Full record

Trial reportJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2016

Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion.

Rieko Takatani, Angelo Molinaro, Giedre Grigelioniene, Olta Tafaj, Tomoyuki Watanabe, Monica Reyes, Amita Sharma, Vibha Singhal, F Lucy Raymond, Agnès Linglart and 1 more

Open access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Bidirectional disruption ofProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
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  11. Article
  12. Article
  13. Article
  14. Molecular Definition of Pseudohypoparathyroidism Variants.The Journal of clinical endocrinology and metabolism · 2021
    Review
  15. Article
  16. A Novel GNAS Duplication Associated With Loss-of-Methylation Restricted to Exon A/B Causes Pseudohypoparathyroidism Type Ib (PHP1B).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Article
  17. Review
  18. Review
  19. Pseudohypoparathyroidism.Endocrinology and metabolism clinics of North America · 2018
    Review
  20. Review
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

11 authors at 4 institutions in 3 countries.

Rieko TakataniEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Angelo MolinaroEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Giedre GrigelionieneEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Olta TafajEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Tomoyuki WatanabeEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Monica ReyesEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Amita SharmaPediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Vibha SinghalPediatric Endocrinology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
F Lucy RaymondDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Agnès LinglartPaediatric Endocrinology and Diabetology, French National Reference Centre for Rare Disorders of Mineral Metabolism, AP-HP Hôpital Bicêtre Paris Sud, le Kremlin-Bicêtre, France.
Harald JüppnerEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Harvard University · USMassachusetts General Hospital · USBicêtre Hospital · FRUniversity of Cambridge · GB

Funding

PTH/PTHRP RECEPTOR DEFECTS IN PSEUDOHYPOPARATHYROIDISMR01DK046718 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JUEPPNER, HARALD W. · 1993 to 2024
$6.0M
Training Program in Nutrition and MetabolismT32HD052961 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI GRINSPOON, STEVEN K. · 2005 to 2016
$1.3M
NICHD NIH HHS T32 HD052961NIDDK NIH HHS R01 DK046718NIDDK NIH HHS R01 DK46718Wellcome Trust 100140
6 · The paper itself

Abstract

Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but it seems unlikely that this disease variant is caused by heterozygous inherited or de novo mutations involving GNAS.

Indexed as

AllelesBase SequenceFamilySequence DeletionAdolescentCell Line, TransformedChildChromograninsDNA MethylationEpigenesis, GeneticExonsFemaleGTP-Binding Protein alpha Subunits, GsHumansMalePseudohypoparathyroidismChromograninsGNAS protein, humanGTP-Binding Protein alpha Subunits, GsSTX16 protein, humanSyntaxin 16EPIGENETICSGNASHORMONAL RESISTANCEPSEUDOHYPOPARATHYROIDISM

Identifiers

PMID26479409
PMCPMC4826817
OpenAlexW2135533495

What OpenQuestion holds

Textmetadata
LicenceTDM
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.