SNORD116 and growth hormone therapy impact IGFBP7 in Prader-Willi syndrome.
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
25
09
2020
accepted:
09
04
2021
revised:
07
04
2021
pubmed:
28
5
2021
medline:
21
10
2021
entrez:
27
5
2021
Statut:
ppublish
Résumé
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS. We collected serum and induced pluripotent stem cells (iPSCs) from GH-treated PWS patients to differentiate into dopaminergic neurons, and in parallel used a Snord116 knockout mouse model. We analyzed the expression of factors potentially linked to GH responsiveness. We found elevated levels of circulating IGFBP7 in naive PWS patients, with IGFBP7 levels normalizing under GHT. We found elevated IGFBP7 levels in the brains of Snord116 knockout mice and in iPSC-derived neurons from a SNORD116-deleted PWS patient. High circulating levels of IGFBP7 in PWS patients may result from both increased IGFBP7 expression and decreased IGFBP7 cleavage, by downregulation of the proconvertase PC1. SNORD116 deletion affects IGFBP7 levels, while IGFBP7 decreases under GHT in PWS patients. Modulation of the IGFBP7 level, which interacts with IGF1, has implications in the pathophysiology and management of PWS under GHT.
Identifiants
pubmed: 34040195
doi: 10.1038/s41436-021-01185-y
pii: S1098-3600(21)05092-9
pmc: PMC8460435
doi:
Substances chimiques
RNA, Small Nucleolar
0
Growth Hormone
9002-72-6
Banques de données
ClinicalTrials.gov
['NCT01298180']
EudraCT
['2008-004612-12']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1664-1672Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK052431
Pays : United States
Informations de copyright
© 2021. The Author(s).
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