An Fgfr2 Mutation as the Underlying Cause of Heritable Osteoporosis: a Case Report

Abstract Osteoporosis is a systemic, multifactorial disorder of bone mineralization. Many factors contributing to the development of osteoporosis have been identified so far, including gender, age, nutrition, lifestyle, exercise, drug use, as well as a range of comorbidities. In addition to environmental and lifestyle factors, molecular-genetic factors account for 60–85% of osteoporosis cases. One of the candidate genes, the pathogenic variants in which are involved in the pathogenesis of osteoporosis is FGFR2. Recently, the key role in development of osteoporosis has been given to molecular-genetic factors. The vitamin D receptor (VDR), collagen type I (COL1), estrogen receptor (ER), apolypoprotein Е (ApoE), bone morphogenetic protein (BMP), and Low-density lipoprotein receptor-related protein 5 (LRP5) are all involved in the pathogenesis of osteoporosis. Additionally, FGFs/FGFRs-dependent signaling has been shown to regulate skeletal development and has been linked to a plethora of heritable disorders of the musculoskeletal system. In this study we present the clinical, biochemical and radiological findings, as well as results of molecular-genetic testing of a 13 year old male patient with heritable osteoporosis, arthralgia and multiple fractures and a family history of bone disease. Whole exome sequencing found a previously undescribed variant in the FGFR2 gene (GRCh37.p13 ENSG00000066468.16: g.123298133dup; ENST00000457416.2:c.722dup; ENSP00000351276.5:p.Asn241LysfsTer43). The same variant was found in affected relatives. These data leads us to believe that the variant in FGFR2 found in our patient and his relatives could be related to their phenotype. Therefore, modern methods of molecular genetic testing can allow us to differentiate between osteogenesis imperfecta and heritable forms of osteoporosis.