An FGFR2 mutation as the potential cause of a new phenotype including early-onset osteoporosis and bone fractures: a case report

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 50-85% of osteoporosis cases. For example, the vitamin D receptor (VDR), collagen type I (COL1), estrogen receptor (ER), apolypoprotein E (ApoE), bone morphogenetic protein (BMP), and Low-density lipoprotein receptor-related protein 5 (LRP5) are all involved in the pathogenesis of osteoporosis. Among the candidate genes, the pathogenic variants in which are involved in the pathogenesis of osteoporosis is FGFR2. 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 proband with heritable osteoporosis, arthralgia and multiple fractures and a family history of abnormal bone mineralization and fractures. Whole exome sequencing found a heterozygous previously undescribed variant in the FGFR2 gene (NM_000141.5) (GRCh37.p13 ENSG00000066468.16: g.123298133dup; ENST00000358487.5:c.722dup; ENSP00000351276.5:p.Asn241LysfsTer43). The same variant was found in two affected relatives. These data lead us to believe that the variant in FGFR2 found in our proband 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 other bone mineralization disorders.

Automated summary

Osteoporosis is a systemic disorder of bone mineralization, influenced by multiple factors including genetics. Variants in the FGFR2 gene have been found to be associated with heritable osteoporosis. Molecular genetic testing can aid in differentiating between osteoporosis and other bone mineralization disorders.