• Uniparental disomy leads to a...

*Result*: Uniparental disomy leads to a novel cause of MC2R-related familial glucocorticoid deficiency type 1.

Title:
Uniparental disomy leads to a novel cause of MC2R-related familial glucocorticoid deficiency type 1.
Authors:
Müller-Nedebock AC; Institute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany., Wenzel E; Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, 04103 Leipzig, Germany.; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, University of Leipzig, 04103 Leipzig, Germany., Pfäffle R; Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, 04103 Leipzig, Germany.
Source:
European journal of endocrinology [Eur J Endocrinol] 2025 Jul 31; Vol. 193 (2), pp. K5-K10.
Publication Type:
Journal Article; Case Reports
Language:
English
Journal Info:
Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE
Imprint Name(s):
Publication: 2023- : Oxford : Oxford University Press
Original Publication: Oslo, Norway : Scandinavian University Press, c1994-
MeSH Terms:
Uniparental Disomy*/genetics , Receptor, Melanocortin, Type 2*/genetics , Steroid Metabolism, Inborn Errors*/genetics , Steroid Metabolism, Inborn Errors*/diagnosis, Receptors, Glucocorticoid/deficiency ; Humans ; Female ; Child ; Metabolism, Inborn Errors
Grant Information:
493646873 German Research Foundation
Contributed Indexing:
Keywords: MC2R; FGD1; UPD 18; exon 1; glucocorticoid deficiency; non-coding
Substance Nomenclature:
0 (Receptor, Melanocortin, Type 2)
0 (Receptors, Glucocorticoid)
SCR Disease Name:
Glucocorticoid Receptor Deficiency
Entry Date(s):
Date Created: 20250729 Date Completed: 20250812 Latest Revision: 20260127
Update Code:
20260130
DOI:
10.1093/ejendo/lvaf152
PMID:
40729435
Database:
MEDLINE

*Further Information*

*Familial glucocorticoid deficiency type 1 (FGD1) is a rare autosomal recessive disease caused by pathogenic variants in the MC2R gene. This case report presents the first documented instance of FGD1 caused by a homozygous 1.421-kb deletion affecting the non-coding promoter region of MC2R. The patient, a 9-year-old girl, presented with severe cortisol insufficiency and hyperpigmentation starting at birth. Genetic testing initially missed the deletion, as standard whole-exome sequencing in 2016 did not include a copy number variation analysis. However, a whole-genome sequencing analysis in 2024 identified the deletion. The variant was inherited through paternal uniparental disomy (UPD), a rare genetic mechanism that caused the homozygous state. This case underscores the value of utilizing current genetic testing approaches, especially in cases where clinical features strongly suggest a genetic etiology despite inconclusive initial genetic testing results. Additionally, it highlights the need to consider non-coding regions and UPD in genetic diagnostics.
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*Conflict of interest: None declared.*