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

Abstract

Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the <i>COL1A1</i> and <i>COL1A2</i> 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 <i>COL1A1</i> and <i>COL1A2</i> 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 <i>PLS3</i>, <i>FN1</i> and <i>COL11A2</i>. A variant in the <i>PLS3</i> gene were identified in the patient, his mother and sister. Since the <i>PLS3</i> gene is located on the X chromosome, the mother and sister showed no signs of the disease. Although the variant in the <i>PLS3</i> 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 <i>PLS3</i> variant of X-linked OI might point to a novel target for personalized therapy in patients with this severe disease.