Novel sonic hedgehog gene variant in a patient with hyponatremia, microsomia, and midline defects; phenotype description in association with a variant of unknown significance [c.755_757del p.(Phe252del)] and an approach to salt-wasting in SHH-related adrenal disorders.
Sonic Hedgehog
hyponatremia
salt-wasting
Journal
Journal of pediatric endocrinology & metabolism : JPEM
ISSN: 2191-0251
Titre abrégé: J Pediatr Endocrinol Metab
Pays: Germany
ID NLM: 9508900
Informations de publication
Date de publication:
27 Jun 2023
27 Jun 2023
Historique:
received:
11
01
2023
accepted:
04
04
2023
medline:
8
6
2023
pubmed:
15
5
2023
entrez:
15
5
2023
Statut:
epublish
Résumé
To contribute a novel sonic hedgehog (SHH) gene variant in association with a novel-meagerly described phenotype and discuss SHH signaling pathway pathology. We present a 5-year-old boy with excessive hyponatremia and natriuresis, microform holoprosencephaly and microsomia, with morphologically intact hypothalamic-pituitary-adrenal (HPA) axis, and hypoaldosteronism, yet without hyperreninemia, hyperkalemia, dehydration episodes, or glucocorticoid insufficiency. Extensive workup excluded common causes of salt-wasting and revealed a novel variant of unknown significance on the sonic hedgehog (SHH) gene; NM_000193.4:c.755_757del (p.Phe252del), in heterozygosity. Salt-wasting in children is predominantly caused by central nervous system lesions, renal tubular dysfunction, or adrenal insufficiency. The SHH protein is a signaling molecule, essential in embryogenesis-including HPA axis differentiation. Inactivating SHH variants disrupt the signaling pathway, leading to dysplasia or dysfunction of target organs. What's new: • We analyze the patient's phenotype in the light of this novel variant • Patient's isolated aldosterone deficiency possibly implies a selective signaling defect affecting the development of adrenal zona glomerulosa • Unexplained hyporeninemia and hypokalemia in the context of hypoaldosteronism raise questions on SHH signaling pathophysiology.
Identifiants
pubmed: 37184081
pii: jpem-2023-0015
doi: 10.1515/jpem-2023-0015
doi:
Substances chimiques
Hedgehog Proteins
0
SHH protein, human
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
608-613Informations de copyright
© 2023 Walter de Gruyter GmbH, Berlin/Boston.
Références
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