JOURNAL ARTICLE

Variants in both the N- or C-terminal domains of IHH lead to defective secretion causing short stature and skeletal defects.

  • Published In: European Journal of Endocrinology, 2024, v. 191, n. 1. P. 38 1 of 3

  • Database: Academic Search Ultimate 2 of 3

  • Authored By: Díaz-González, Francisca; Sentchordi-Montané, Lucía; Lucas-Castro, Elsa; Modamio-Høybjør, Silvia; Heath, Karen E 3 of 3

Abstract

This article focuses on the functional characterization of heterozygous variants in the Indian Hedgehog gene (IHH) associated with short stature and brachydactyly. The study demonstrates that variants located in both the N-terminal and C-terminal domains of IHH significantly reduce secretion of the active N-terminal peptide (IHH-N) and decrease intracellular levels of IHH peptides, impairing protein function. Importantly, this work provides the first evidence that C-terminal domain variants, previously classified as variants of uncertain significance (VUS), affect IHH secretion and contribute to skeletal phenotypes. The authors developed a simple in vitro secretion assay that can help determine the pathogenicity of IHH variants, supporting their role in growth disorders and highlighting the IHH signaling pathway as a potential therapeutic target.

Additional Information

  • Source:European Journal of Endocrinology. 2024/07, Vol. 191, Issue 1, p38
  • Document Type:Article
  • Subject Area:Health and Medicine
  • Publication Date:2024
  • ISSN:0804-4643
  • DOI:10.1093/ejendo/lvae072
  • Accession Number:178778944
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