The LDL receptor-related protein 5 (LRP5) gene has been shown to be involved in both osteoporosis-pseudoglioma syndrome and the high-bone-mass phenotype and turned out to be an important regulator of peak bone mass in vertebrates.
Rheumatologists must be aware of LRP5 gene that in addition to being a major gene in the mendelian disease that is OPPG syndrome seems to be involved in osteoporosis in the general population through some of its polymorphisms.
Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signaling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading.
Mutation of human LRP5 is responsible for osteoporosis-pseudoglioma syndrome and disruption of Lrp6 in mice causes similar effects to mutation of several different Wnt genes.
The Wnt pathway was found to be involved in bone biology in 2001-2002 with the discovery of a (G171V) mutation in the lipoprotein receptor-related protein 5 (LRP5) that resulted in high bone mass and another mutation that completely inactivated Lrp5 function and resulted in osteoporosis pseudoglioma syndrome (OPPG).
In humans, loss of LRP5 function causes osteoporosis-pseudoglioma syndrome, which is characterized by congenital blindness and extremely severe childhood-onset osteoporosis (lumbar spine Z-score often < -4) with fractures.
Mutations in the LRP5 gene causing high bone mass (HBM) and osteoporosis-pseudoglioma (OPPG) underscored the role of the Wnt-LRP5 canonical signaling on bone formation.
Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive condition of congenital blindness and severe childhood osteoporosis with skeletal fragility, caused by loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene.
The TCIRG1 gene was shown to underly autosomal recessive osteopetrosis (ARO), and, recently, mutations in the LRP5 gene were found both in the osteoporosis-pseudoglioma syndrome and the high bone mass trait.
Osteoporosis-pseudoglioma sydrome (OPPG) is an autosomal recessive disorder with early-onset severe osteoporosis and blindness, caused by biallelic loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene.
The authors report a case of familial exudative vitreoretinopathy in the spectrum of osteoporosis pseudoglioma syndrome associated with novel mutations of the LRP5 and TSPAN12 genes that resulted in a phenotype similar to bilateral persistent fetal vasculature.
We looked for a mutation in the LRP5 gene in two brothers (12 and 4 years old) with clinical features of OPPG (blindness, low BMD and fragility fractures) and in their consanguineous parents to confirm the diagnosis of OPPG.
These results rule out a direct function of Lrp5 in osteoblast progenitor cells and add further support to the notion that dysregulation of serotonin synthesis is involved in bone mass abnormalities observed in OPPG patients.
Osteoporosis pseudoglioma syndrome (OPPGS) is a rare autosomal recessive genetic disorder characterised by congenital blindness and osteoporosis, caused by biallelic mutations in the LRP5 gene.
The recent identification of a link between bone mass in humans and gain- or loss-of-function mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (osteoporosis pseudoglioma syndrome, high bone mass trait) or in the Wnt antagonist sclerostin (sclerosteosis, van Buchem syndrome) has called the attention of academic and industry scientists and clinicians to the importance of this signaling pathway in skeletal biology and disease.
Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness, due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene.
The gene encoding the low-density lipoprotein receptor-related protein 5 (LRP5) gene has recently been shown to affect bone mass accrual during growth and to be involved in osteoporosis-pseudoglioma syndrome and a high bone mass phenotype.
Loss of function of Sost or treatment with a Sclerostin neutralizing antibody improves bone properties in animal models of Osteoporosis Pseudoglioma syndrome (OPPG), likely due to action through the LRP6 receptor, which suggests patients may benefit from these therapies.