Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ekhzaimy, Aishah A., Alyusuf, Ebtihal Y., Alswailem, Meshael, Alzahrani, Ali S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784658733674004480
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
work_keys_str_mv AT ekhzaimyaishaha anovelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT alyusufebtihaly anovelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT alswailemmeshael anovelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT alzahranialis anovelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT ekhzaimyaishaha novelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT alyusufebtihaly novelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT alswailemmeshael novelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin
AT alzahranialis novelmutationinagenecausessclerosteosisinafamilyofmediterraneanorigin