X-linked osteoporosis/osteogenesis imperfecta due to a PLS3 mutation: the first description in Russia

The differential diagnosis of osteoporosis in children and young adults is a challenge. In young people, the most common cause of primary osteoporosis is osteogenesis imperfecta (OI). In 2013, 5 families with X-linked osteoporosis and osteoporotic fractures manifesting in childhood were described for the first time in men who had pathogenic variants in the PLS3 gene. The PLS3 gene is located on the X chromosome (Xq23) and encodes the protein plastin 3, the main function of which is to bind and group F-actin molecules, the main component of the cytoskeleton. Currently, about 50 men with this disease have been described in the literature. In this article, two brothers with X-linked osteoporosis/OI are described, in whom hemizygous mutations in the PLS3 gene ((NM_005032.7) c.836_837dup (p.His280Phefs*43) were detected. In both brothers, fractures have occurred since childhood (forearm bones, and in the elder brother also a fracture of the humerus and a fracture of the greater trochanter), and later multiple compression fractures of the vertebrae were detected. No disorders of mineral metabolism were detected in both brothers, but bone mineral density (BMD) measured by DEXA was decreased. The elder brother is treated with teriparatide, the younger brother is treated with zoledronic acid, and new fractures were not detected during a short follow-up. Both brothers received this PLS3 variant from their mother, in whom it was heterozygous. She was diagnosed with primary hyperparathyroidism with multiple parathyroid adenomas and severe osteoporosis with two thoracic vertebral compression fractures and decrease in spinal BMD. In Russia, cases of X-linked osteoporosis/OI due to mutations in the PLS3 gene have not been previously described. Cases of primary hyperparathyroidism in patients with PLS3 mutations have not been described in the literature.