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A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin
Background and Objectives: Sclerostin is an SOST gene product that inhibits osteoblast activity and prevents excessive bone formation by antagonizing the Wnt signaling pathway. Sclerosteosis has been linked to loss of function mutations in the SOST gene. It is a rare autosomal recessive disorder cha...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878747/ https://www.ncbi.nlm.nih.gov/pubmed/35208525 http://dx.doi.org/10.3390/medicina58020202 |
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author | Ekhzaimy, Aishah A. Alyusuf, Ebtihal Y. Alswailem, Meshael Alzahrani, Ali S. |
author_facet | Ekhzaimy, Aishah A. Alyusuf, Ebtihal Y. Alswailem, Meshael Alzahrani, Ali S. |
author_sort | Ekhzaimy, Aishah A. |
collection | PubMed |
description | Background and Objectives: Sclerostin is an SOST gene product that inhibits osteoblast activity and prevents excessive bone formation by antagonizing the Wnt signaling pathway. Sclerosteosis has been linked to loss of function mutations in the SOST gene. It is a rare autosomal recessive disorder characterized by craniotubular hyperostosis and can lead to fatal cerebellar herniation. Our aim is to describe the clinical and radiological features and the new underlying SOST mutation in a patient with sclerosteosis. Case: A 25-year-old female who was referred to the endocrine clinic for suspected excess growth hormone. The patient complained of headaches, progressive blurred vision, hearing disturbances, increased size of feet, proptosis, and protrusion of the chin. She had normal antenatal history except for syndactyly. Images showed diffuse osseous thickening and high bone mineral density. Biochemical and hormonal tests were normal. Due to progressive compressive optic neuropathy, optic nerve fenestration with decompression hemicraniotomy was performed. Sclerosteosis was suspected due to the predominant craniotubular hyperostosis with syndactyly. Using peripheral leucocyte DNA, genomic sequencing of the SOST gene was performed. This identified a novel deletion homozygous mutation in the SOST gene (c.387delG, p.Asp131ThrfsTer116) which disrupts sclerostin function, causing sclerosteosis. Conclusions: Discovery of the molecular basis of sclerosteosis represents an important advance in the diagnosis and management of this fatal disease. |
format | Online Article Text |
id | pubmed-8878747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88787472022-02-26 A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin Ekhzaimy, Aishah A. Alyusuf, Ebtihal Y. Alswailem, Meshael Alzahrani, Ali S. Medicina (Kaunas) Case Report Background and Objectives: Sclerostin is an SOST gene product that inhibits osteoblast activity and prevents excessive bone formation by antagonizing the Wnt signaling pathway. Sclerosteosis has been linked to loss of function mutations in the SOST gene. It is a rare autosomal recessive disorder characterized by craniotubular hyperostosis and can lead to fatal cerebellar herniation. Our aim is to describe the clinical and radiological features and the new underlying SOST mutation in a patient with sclerosteosis. Case: A 25-year-old female who was referred to the endocrine clinic for suspected excess growth hormone. The patient complained of headaches, progressive blurred vision, hearing disturbances, increased size of feet, proptosis, and protrusion of the chin. She had normal antenatal history except for syndactyly. Images showed diffuse osseous thickening and high bone mineral density. Biochemical and hormonal tests were normal. Due to progressive compressive optic neuropathy, optic nerve fenestration with decompression hemicraniotomy was performed. Sclerosteosis was suspected due to the predominant craniotubular hyperostosis with syndactyly. Using peripheral leucocyte DNA, genomic sequencing of the SOST gene was performed. This identified a novel deletion homozygous mutation in the SOST gene (c.387delG, p.Asp131ThrfsTer116) which disrupts sclerostin function, causing sclerosteosis. Conclusions: Discovery of the molecular basis of sclerosteosis represents an important advance in the diagnosis and management of this fatal disease. MDPI 2022-01-28 /pmc/articles/PMC8878747/ /pubmed/35208525 http://dx.doi.org/10.3390/medicina58020202 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Ekhzaimy, Aishah A. Alyusuf, Ebtihal Y. Alswailem, Meshael Alzahrani, Ali S. A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin |
title | A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin |
title_full | A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin |
title_fullStr | A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin |
title_full_unstemmed | A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin |
title_short | A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin |
title_sort | novel mutation in a gene causes sclerosteosis in a family of mediterranean origin |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878747/ https://www.ncbi.nlm.nih.gov/pubmed/35208525 http://dx.doi.org/10.3390/medicina58020202 |
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