Skip to content
DraconiticResearch
Search Sources API
194,161 studies31 sourcesUpdated 37 min ago
Peer-reviewedCC BYBMC Medical Genomics

Genetic evidence linking the promoter region and 5’-UTR deletion of GNAS with pseudohypoparathyroidism type 1 C

  • Chung Lee1
  • Yoon Ji Ahn2
  • Sung-Chul Jung3
  • Saeyoung Park3
  • Ji Yeon Kim4
  • Chang-Seok Ki5
  • Woong-Yang Park6
  • Sung Yoon Cho2
6 affiliations
  1. 1Department of Pathology, Yonsei University College of Medicine
  2. 2Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine
  3. 3Department of Biochemistry, College of Medicine, Ewha Womans University
  4. 4Department of Biomedical Science, CHA Stem Cell Institute, CHA University
  5. 5GC Genome
  6. 6Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine
Read full textDOICite

Abstract

Background Pseudohypoparathyroidism (PHP) is a heterogeneous disorder caused by genetic or epigenetic changes at the GNAS locus on chromosome 20q13.3 leading to impaired cyclic adenosine monophosphate (cAMP)-dependent signaling pathway via the alpha-subunit of the stimulatory G protein (Gsα). Unlike PHP type 1 A (PHP1A), which occurs due to GNAS variant and low Gsα activity, the activity of Gsα is normal in PHP type 1 C (PHP1C) despite the same phenotypic characteristics as PHP1A. However, the genetic cause of PHP1C is unknown. Methods The likely causative variant of PHP1C was investigated using next-generation sequencing, and Gsα protein levels and function were assessed in patient-derived cells by immunoblotting, immunocytochemistry and cAMP measurement. Results We identified a de novo genomic deletion in a promoter region and 5’ untranslated region (UTR) of GNAS (5’ deletion of GNAS), in a participant with PHP1C. Furthermore, although the mRNA and protein levels of GNAS were maintained, cAMP production was impaired in PHP1C, implicating a functional abnormality rather than quantitative changes. Conclusions This novel 5’-UTR deletion of GNAS may underlie PHP1C and highlights the importance of assessing non-coding regions of GNAS in participants with PHP1C or PHP1A who lack pathogenic variants in conventional genetic tests.

Related

  1. Loneliness as a pathway linking hearing decline to cognitive aging: Longitudinal and genetic evidence.
    Shuai Yang, Matthew D Grilli, Robyn E Wootton +4
    Alzheimer's & dementia : the journal of the Alzheimer's AssociationPeer-reviewedCC BY-NC-NDFull textNeuroscienceEurope PMCPMC
  2. Genetic Evidence Linking Prefrontal Surface Area to ADHD, Major Depression, and Smoking Initiation
    rui wang, Yifan Du, Yunkai Yang
    PsyArXivPreprintCC BY 4.0Full textNeurosciencePsychiatry & mental healthOSF
  3. ProFinder: Candidate constitutive promoter prediction across the bacterial tree for genetic tool development in non-model species
    A. Gautam, J. W. Marsh
    bioRxivPreprintAll rights reservedFull textMicrobiologybioRxiv
  4. Mobile genetic elements drive a plasmid fusion and deletion lifecycle shaping evolution and antimicrobial resistance
    Thomas Ipoutcha, Yiqing Wang, Eduardo P C Rocha +1
    Nature CommunicationsPeer-reviewedCC BY 4.0Full text1 citedMicrobiologyHALEurope PMC
  5. Deletion of Major Endoxylanase Genes in Fusarium graminearum Uncovers Distinct Virulence Phenotypes Influenced by the Genetic Background
    Arianna Panichi, Silvana Odorizzi, Carla Castiglioni +5
    Molecular Plant PathologyPeer-reviewedCC BY 4.0Full textCell biologyPMC

Cite

BibTeXRIS
BibTeX
@article{lee2026genetic,
  title = {{Genetic evidence linking the promoter region and 5’-UTR deletion of GNAS with pseudohypoparathyroidism type 1 C}},
  author = {Chung Lee and Yoon Ji Ahn and Sung-Chul Jung and Saeyoung Park and Ji Yeon Kim and Chang-Seok Ki and Woong-Yang Park and Sung Yoon Cho},
  journal = {BMC Medical Genomics},
  year = {2026},
  month = jul,
  doi = {10.1186/s12920-026-02439-x},
  url = {https://doi.org/10.1186/s12920-026-02439-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Genetic evidence linking the promoter region and 5’-UTR deletion of GNAS with pseudohypoparathyroidism type 1 C
AU  - Chung Lee
AU  - Yoon Ji Ahn
AU  - Sung-Chul Jung
AU  - Saeyoung Park
AU  - Ji Yeon Kim
AU  - Chang-Seok Ki
AU  - Woong-Yang Park
AU  - Sung Yoon Cho
PY  - 2026
DA  - 2026/07/01
JO  - BMC Medical Genomics
DO  - 10.1186/s12920-026-02439-x
UR  - https://doi.org/10.1186/s12920-026-02439-x
AB  - Background Pseudohypoparathyroidism (PHP) is a heterogeneous disorder caused by genetic or epigenetic changes at the GNAS locus on chromosome 20q13.3 leading to impaired cyclic adenosine monophosphate (cAMP)-dependent signaling pathway via the alpha-subunit of the stimulatory G protein (Gsα). Unlike PHP type 1 A (PHP1A), which occurs due to GNAS variant and low Gsα activity, the activity of Gsα is normal in PHP type 1 C (PHP1C) despite the same phenotypic characteristics as PHP1A. However, the genetic cause of PHP1C is unknown. Methods The likely causative variant of PHP1C was investigated using next-generation sequencing, and Gsα protein levels and function were assessed in patient-derived cells by immunoblotting, immunocytochemistry and cAMP measurement. Results We identified a de novo genomic deletion in a promoter region and 5’ untranslated region (UTR) of GNAS (5’ deletion of GNAS), in a participant with PHP1C. Furthermore, although the mRNA and protein levels of GNAS were maintained, cAMP production was impaired in PHP1C, implicating a functional abnormality rather than quantitative changes. Conclusions This novel 5’-UTR deletion of GNAS may underlie PHP1C and highlights the importance of assessing non-coding regions of GNAS in participants with PHP1C or PHP1A who lack pathogenic variants in conventional genetic tests.
SN  - 1755-8794
ER  -