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Müller-Nedebock, A.C.* ; Wenzel, E. ; Pfäffle, R.*

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

Eur. J. Endocrinol. 193, K5-K10 (2025)
DOI PMC
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mc2r ; Fgd1 ; Glucocorticoid Deficiency ; Upd 18 ; Non-coding; Acth Receptor; Mutations; Promoter
ISSN (print) / ISBN 0804-4643
e-ISSN 1479-683X
Zeitschrift European Journal of Endocrinology
Quellenangaben Band: 193, Heft: 2, Seiten: K5-K10 Artikelnummer: , Supplement: ,
Verlag BioScientifica
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen German Research Foundation
AI-assisted technologies in the writing process