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Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant

Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the cur...

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Autores principales: Merkuryeva, Elena, Markova, Tatiana, Tyurin, Anton, Valeeva, Diana, Kenis, Vladimir, Sumina, Maria, Sorokin, Igor, Shchagina, Olga, Skoblov, Mikhail, Nefedova, Maria, Khusainova, Rita, Zakharova, Ekaterina, Dadali, Elena, Kutsev, Sergey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178575/
https://www.ncbi.nlm.nih.gov/pubmed/37175737
http://dx.doi.org/10.3390/ijms24098021
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author Merkuryeva, Elena
Markova, Tatiana
Tyurin, Anton
Valeeva, Diana
Kenis, Vladimir
Sumina, Maria
Sorokin, Igor
Shchagina, Olga
Skoblov, Mikhail
Nefedova, Maria
Khusainova, Rita
Zakharova, Ekaterina
Dadali, Elena
Kutsev, Sergey
author_facet Merkuryeva, Elena
Markova, Tatiana
Tyurin, Anton
Valeeva, Diana
Kenis, Vladimir
Sumina, Maria
Sorokin, Igor
Shchagina, Olga
Skoblov, Mikhail
Nefedova, Maria
Khusainova, Rita
Zakharova, Ekaterina
Dadali, Elena
Kutsev, Sergey
author_sort Merkuryeva, Elena
collection PubMed
description Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the current classification of skeletal disorders, the disease is included in the group of bone fragility disorders along with osteogenesis imperfecta. The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis—the main lipid component of the plasma membrane essential for bone mineralization. To date, 15 patients from eight families with CDL with bone fragility have been described in the literature, and a recurrent variant c.148C>T (p.Arg50Ter) in the SGMS2 gene has been identified, which was found in patients from six families. We diagnosed the disease in 11 more patients from three unrelated families, caused by the same heterozygous nonsense variant c.148C>T (p.Arg50Ter) in the SGMS2 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the SGMS2 gene, the presence of which must be taken into consideration in the diagnosis of the disease. The primary analysis of this variant will contribute to optimal molecular genetic diagnostics, which can reduce diagnostic costs and time.
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spelling pubmed-101785752023-05-13 Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant Merkuryeva, Elena Markova, Tatiana Tyurin, Anton Valeeva, Diana Kenis, Vladimir Sumina, Maria Sorokin, Igor Shchagina, Olga Skoblov, Mikhail Nefedova, Maria Khusainova, Rita Zakharova, Ekaterina Dadali, Elena Kutsev, Sergey Int J Mol Sci Article Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the current classification of skeletal disorders, the disease is included in the group of bone fragility disorders along with osteogenesis imperfecta. The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis—the main lipid component of the plasma membrane essential for bone mineralization. To date, 15 patients from eight families with CDL with bone fragility have been described in the literature, and a recurrent variant c.148C>T (p.Arg50Ter) in the SGMS2 gene has been identified, which was found in patients from six families. We diagnosed the disease in 11 more patients from three unrelated families, caused by the same heterozygous nonsense variant c.148C>T (p.Arg50Ter) in the SGMS2 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the SGMS2 gene, the presence of which must be taken into consideration in the diagnosis of the disease. The primary analysis of this variant will contribute to optimal molecular genetic diagnostics, which can reduce diagnostic costs and time. MDPI 2023-04-28 /pmc/articles/PMC10178575/ /pubmed/37175737 http://dx.doi.org/10.3390/ijms24098021 Text en © 2023 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
Merkuryeva, Elena
Markova, Tatiana
Tyurin, Anton
Valeeva, Diana
Kenis, Vladimir
Sumina, Maria
Sorokin, Igor
Shchagina, Olga
Skoblov, Mikhail
Nefedova, Maria
Khusainova, Rita
Zakharova, Ekaterina
Dadali, Elena
Kutsev, Sergey
Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
title Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
title_full Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
title_fullStr Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
title_full_unstemmed Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
title_short Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
title_sort clinical and genetic characteristics of calvarial doughnut lesions with bone fragility in three families with a reccurent sgms2 gene variant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178575/
https://www.ncbi.nlm.nih.gov/pubmed/37175737
http://dx.doi.org/10.3390/ijms24098021
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