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X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3

Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the COL1A1 and COL1A2 genes. Recent molecular studies of the network of signaling pathways have contributed to a better understanding of bone remodeling and the...

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Autores principales: Brlek, Petar, Antičević, Darko, Molnar, Vilim, Matišić, Vid, Robinson, Kristina, Aradhya, Swaroop, Krpan, Dalibor, Primorac, Dragan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701009/
https://www.ncbi.nlm.nih.gov/pubmed/34946798
http://dx.doi.org/10.3390/genes12121851
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author Brlek, Petar
Antičević, Darko
Molnar, Vilim
Matišić, Vid
Robinson, Kristina
Aradhya, Swaroop
Krpan, Dalibor
Primorac, Dragan
author_facet Brlek, Petar
Antičević, Darko
Molnar, Vilim
Matišić, Vid
Robinson, Kristina
Aradhya, Swaroop
Krpan, Dalibor
Primorac, Dragan
author_sort Brlek, Petar
collection PubMed
description Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the COL1A1 and COL1A2 genes. Recent molecular studies of the network of signaling pathways have contributed to a better understanding of bone remodeling and the pathogenesis of OI caused by mutations in many other genes associated with normal bone mineralization. In this paper, a case of a rare X-linked variant of OI with a change in the gene encoding plastin 3—a protein important for the regulation of the actin cytoskeleton, is presented. A 16-year-old patient developed ten bone fractures caused by minor trauma or injury, including a compression fracture of the second lumbar vertebra during his lifetime. Next-generation sequencing analysis did not show pathologically relevant deviations in the COL1A1 and COL1A2 genes. Targeted gene analyses (Skeletal disorder panel) of the patient, his father, mother and sister were then performed, detecting variants of uncertain significance (VUS) for genes PLS3, FN1 and COL11A2. A variant in the PLS3 gene were identified in the patient, his mother and sister. Since the PLS3 gene is located on the X chromosome, the mother and sister showed no signs of the disease. Although the variant in the PLS3 gene (c.685G>A (p.Gly229Arg)) has not yet been described in the literature, nor is its pathogenicity known, clinical findings combined with genetic testing showed that this variant may explain the cause of X-linked OI in our patient. This rare case of the PLS3 variant of X-linked OI might point to a novel target for personalized therapy in patients with this severe disease.
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spelling pubmed-87010092021-12-24 X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3 Brlek, Petar Antičević, Darko Molnar, Vilim Matišić, Vid Robinson, Kristina Aradhya, Swaroop Krpan, Dalibor Primorac, Dragan Genes (Basel) Article Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the COL1A1 and COL1A2 genes. Recent molecular studies of the network of signaling pathways have contributed to a better understanding of bone remodeling and the pathogenesis of OI caused by mutations in many other genes associated with normal bone mineralization. In this paper, a case of a rare X-linked variant of OI with a change in the gene encoding plastin 3—a protein important for the regulation of the actin cytoskeleton, is presented. A 16-year-old patient developed ten bone fractures caused by minor trauma or injury, including a compression fracture of the second lumbar vertebra during his lifetime. Next-generation sequencing analysis did not show pathologically relevant deviations in the COL1A1 and COL1A2 genes. Targeted gene analyses (Skeletal disorder panel) of the patient, his father, mother and sister were then performed, detecting variants of uncertain significance (VUS) for genes PLS3, FN1 and COL11A2. A variant in the PLS3 gene were identified in the patient, his mother and sister. Since the PLS3 gene is located on the X chromosome, the mother and sister showed no signs of the disease. Although the variant in the PLS3 gene (c.685G>A (p.Gly229Arg)) has not yet been described in the literature, nor is its pathogenicity known, clinical findings combined with genetic testing showed that this variant may explain the cause of X-linked OI in our patient. This rare case of the PLS3 variant of X-linked OI might point to a novel target for personalized therapy in patients with this severe disease. MDPI 2021-11-23 /pmc/articles/PMC8701009/ /pubmed/34946798 http://dx.doi.org/10.3390/genes12121851 Text en © 2021 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 Article
Brlek, Petar
Antičević, Darko
Molnar, Vilim
Matišić, Vid
Robinson, Kristina
Aradhya, Swaroop
Krpan, Dalibor
Primorac, Dragan
X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3
title X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3
title_full X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3
title_fullStr X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3
title_full_unstemmed X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3
title_short X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3
title_sort x-linked osteogenesis imperfecta possibly caused by a novel variant in pls3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701009/
https://www.ncbi.nlm.nih.gov/pubmed/34946798
http://dx.doi.org/10.3390/genes12121851
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