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

• Published in: International journal of molecular sciences Vol. 24; no. 9; p. 8021
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.04.2023; MDPI
• Subjects: Age; Back pain; Bone dysplasia; bone fractures; Bone mineral density; Bones; Calcification, Physiologic; Enzymes; Fractures; Fractures, Bone - genetics; Fragility; Genetic variability; Hereditary diseases; Heterozygote; Humans; Laboratories; Lesions; Lipids; low bone mineral density; Medical imaging; Metabolism; Mineralization; Osteochondrodysplasias; Osteogenesis; Osteogenesis imperfecta; Osteogenesis Imperfecta - genetics; Osteoporosis; Patients; Phosphatase; SGMS2 gene; Sphingomyelin; Spondylometaphyseal dysplasia; Vertebrae; Wrist; bone fractures; SGMS2 gene; low bone mineral density
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24098021

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 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 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 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the 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.