| Autor: |
Shuaa Basalom, Mélissa Fiscaletti, Valancy Miranda, Céline Huber, Guillaume Couture, Régen Drouin, Élise Monceau, Sandrine Wavrant, Johanne Dubé, Outi Mäkitie, Valérie Cormier-Daire, Philippe M. Campeau |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Bone Reports, Vol 15, Iss , Pp 101121- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2352-1872 |
| DOI: |
10.1016/j.bonr.2021.101121 |
| Popis: |
Calvarial Doughnut Lesions with Bone Fragility (CDL) is an autosomal dominant genetic disease, characterized by low bone mineral density, multiple fractures starting in childhood, and sclerotic doughnut-shaped lesions in the cranial bones. Aubé and colleagues described in 1988 a French-Canadian family of 12 affected members who had a clinical diagnosis of doughnut lesions of the skull, with pathological fractures, osteopenia, “bone in bone” in the vertebral bodies and squaring of metatarsal and metacarpal bones. Herein we study new members of this family. Sequential genetic testing identified a nonsense variant c.148C>T, p. Arg50⁎ in SGMS2 previously reported in other families. SGMS2 encodes Sphingomyelin Synthase 2, which produces Sphingomyelin (SM), a major lipid component of the plasma membrane that plays a role in bone mineralization. The nonsense variant is associated with milder phenotype. The proband presents with bone in bone vertebral appearance that had been defined uniquely in the first cases described in the same family. The proband's son was identified to carry the same variant, which makes him the sixth generation with the diagnosis of CDL. We also report that the same pathogenic variant was identified in another previously described family, from France. These reports further confirm the genetic basis of CDL, the recurrence of the same variant (p.Arg50*) in individuals of the same ancestry, and the variable penetrance of some of the clinical findings. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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