Аннотация:ObjectivePlastin-3 (PLS3) functions as an actin-binding protein which isinvolved in cytoskeleton remodeling. In bone, plastin-3 is part ofthe mechanosensitive mechanism of osteocytes and is involvedin the mineralization process. We present clinical cases of two brothers with novel PLS3 variants.MethodsWhole-exome sequencing was performed on G400 (BGI, China) toidentify the cause of bone fragility.ResultsTwo brothers were referred due to bone fragility.Patient 1, 20 y.o. suffered from multiple fractures starting fromage 6 when bilateral forearm fractures occured. At age 15 multiplevertebral fractures (VFs) and a patellar fracture were diagnosed.DXA showed low BMD: L1-L4 -4.8SD, femoral neck -3.9SD, hip-4.2SD Z-score. Secondary causes of osteoporosis were exclud-ed. This patient received levothyroxine 100mkg due to congenitalhypothyroidism. At age 19 multiple Th2-8, 11-12, L1-5 VFs werediagnosed, along with elevated osteocalcin 94.89 ng/mL (24-70),CTx 1.56 ng/mL (0.1-0.85), alkaline phosphatase 204 IU/L (40-150). Treatment with zoledronic acid 5 mg was initiated. A yearlater DXA showed BMD improvement: L1-L4 -4.2SD, femoral neck-2.6SD, total hip -2.6SD Z-score, no new VFs or non-vertebral frac-tures were detected. One more infusion of zoledronic acid 5 mgwas given.Patient 2, 38 y.o. suffered multiple fractures (forearm bones,proximal humerus, ribs, metacarpal and metatarsal bones, mul-tiple VFs, greater trochanteric fracture) from age 10. Secondarycauses of osteoporosis were excluded. At age 35, this patient re-ceived zoledronic acid 5 mg. At age 37, DXA results were: L1-L4-2.4SD, neck -2.3SD, hip -2.6SD Z-score. CT showed new VFs Th4-12, L1-L5. Teriparatide 20 µg daily was prescribed. A year laterDXA did not show improvement, however no new fractures wererecorded.Both brothers had normal height, no visual bone deformitiesor blue sclera. Exome sequencing revealed a novel most likelypathogenic variant in PLS3 (NM_005032/7) c.836_837dup (p.Hi-s280Phefs*43) which has not been previously described in theliterature.Conclusion: A novel PLS3 variant in two brothers with multipleVFs and non-vertebral fractures adds to the description of thisrare osteogenesis imperfecta with multiple fractures starting ina late childhood which may be successfully treated by zoledronicacid or teriparatide.
