Evidence map›Paper›PMID 34791361›Full record

ArticleThe Journal of clinical endocrinology and metabolism2022

Lack of GNAS Remethylation During Oogenesis May Be a Cause of Sporadic Pseudohypoparathyroidism Type Ib.

Angelo Milioto, Monica Reyes, Patrick Hanna, Zentaro Kiuchi, Serap Turan, Daniel Zeve, Chhavi Agarwal, Giedre Grigelioniene, Ang Chen, Veronica Mericq and 6 more

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

Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

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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

16 authors at 11 institutions in 5 countries.

Angelo MiliotoEndocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Monica ReyesEndocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Patrick HannaEndocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4998-2901
Zentaro KiuchiEndocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Serap TuranDepartment of Pediatric Endocrinology, Marmara University School of Medicine, Istanbul, Turkey.ORCID 0000-0002-5172-5402
Daniel ZeveDivision of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
Chhavi AgarwalPediatric Endocrinology of New York, Scarsdale, NY, USA.
Giedre GrigelionieneDepartment of Molecular Medicine and Surgery, Karolinska Institutet, and Department of Clinical Genetics, Karolinska University Hospital Stockholm, Stockholm, Sweden.
Ang ChenAny Chen, Arizona Kidney Disease and Hypertension Center, Flagstaff, AZ, USA.
Veronica MericqInstitute of Maternal and Child Research (IDIMI), University of Chile, Santiago, Chile.
Myrto FrangosChildren's Endocrine Care, St. Louis, MO, USA.
Svetlana TenConsultant of Pediatric Endocrinology, Richmond University Medical Center, Staten Island, NY, USA.ORCID 0000-0002-2565-0400
Giovanna MantovaniEndocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0002-9065-3886
Isidro B SaluskyDivision of Nephrology, Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Peter TebbenDepartment of Internal Medicine and Pediatrics, Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA.
Harald JüppnerEndocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7491-0515
Harvard University · USBoston Children's Hospital · USColorado Kidney Care · USKarolinska University Hospital · SEMarmara University · TRMayo Clinic in Arizona · USRichmond University Medical Center · USScarsdale Historical Society · USUniversity of California, Los Angeles · USUniversity of Chile · CLUniversity of Milan · IT

Funding

NIDDK NIH HHS
6 · The paper itself

Abstract

contextPseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B. In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown.

objectiveDetermine whether PHP1B encountered after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) causes GNAS remethylation defects similar to those in sporPHP1B.

designRetrospective analysis.

resultsNine among 36 sporPHP1B patients investigated since 2000, all with loss of methylation (LOM) at the 3 maternal GNAS differentially methylated regions (DMRs) and gain of methylation at the paternal NESP DMR, had been conceived through IVF or ICSI. Besides abnormal GNAS methylation, IVF/ICSI PHP1B cases revealed no additional imprinting defects. Three of these PHP1B patients have dizygotic twins, and 4 have IVF/ICSI-conceived siblings, all with normal GNAS methylation; 2 unaffected younger siblings were conceived naturally.

conclusionSporadic and IVF/ICSI-conceived PHP1B patients revealed indistinguishable epigenetic changes at all 4 GNAS DMRs, thus suggesting a similar underlying disease mechanism. Given that remethylation at the 3 maternal DMRs occurs during oogenesis, male factors are unlikely to cause LOM postfertilization. Instead, at least some of the sporPHP1B variants could be caused by a defect or defects in an oocyte-expressed gene that is required for fertility and for re-establishing maternal GNAS methylation imprints. It remains uncertain, however, whether the lack of GNAS remethylation alone and the resulting reduction in Gsα expression is sufficient to impair oocyte maturation.

Indexed as

ChromograninsPseudohypoparathyroidismDNA MethylationGTP-Binding Protein alpha Subunits, GsHumansMaleOogenesisRetrospective StudiesChromograninsGNAS protein, humanGTP-Binding Protein alpha Subunits, GscalciumepigeneticsGNAS methylationGs-alphaGsαICSIintracytoplasmic sperm injectionin vitro fertilizationIVFphosphatePHP1Bpseudohypoparathyroidism type IbPTHSTX16-GNAS

Identifiers

PMID34791361
PMCPMC8947795
OpenAlexW3213803241

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.