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“The unbreakable bones mutation”
The Good: This mutation provides stronger than average bones (higher bone densities) and is therefore dubbed as the “stronger bones” or exaggerated as the “unbreakable bones” mutation.
The reality: Mutations within the gene are known to lead to various bone disorders, including high bone mass (HBM), and homozygous loss-of-function mutations caused by osteoporosis syndrome (OPPG). This syndrome is characterized by early-onset osteoporosis and complications in eye development. In experiments with mice, the LRP5 mutation expressed a low bone mass phenotype. They also exhibited decreased osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization. Furthermore, associations have also been reported between the LRP5 gene and polymorphisms (negatively affecting bone mass and size) in those affected by the mutation.-1 These mutations can directly cause a loss of function (in the) low-density lipoprotein receptor…(LRP5) of its inhibitor Sclerostin (SOST). LRP5 mutations reduce “Wnt signaling” that causes many disorders, including childhood-onset osteoporosis called “Idiopathic juvenile osteoporosis” (IJO)-2. The first symptoms of IJO appear well before puberty, and the main symptoms include reduced bone mineral density (BMD), vertebral compression fractures, and metaphyseal fractures in the long bones. The fractures lead to bone pain and impaired mobility [1–3]. Researchers report that this mutation exhibits “dangerous and unwanted side effects.” The mutation can be inherited in an autosomal dominant manner (meaning the carriers receive two mutations), which increases the likelihood of degradative side effects-3
Our results provide additional information on the role of LRP5 mutations and their effects on the development of juvenile-onset primary osteoporosis, and hence the pathogenesis of the disorder. The mutations causing primary osteoporosis…may therefore result in decreased bone formation.
All LRP5 mutations associated with primary osteoporosis …(were) located in the coding regions of the LRP5 gene.
Korvala, J., Jüppner, H., Mäkitie, O. et al. Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity. BMC Med Genet 13, 26 (2012). https://doi.org/10.1186/1471-2350-13-26
Summary: While the genetic mutation to the LRP5 gene does render the benefit of an increased density in bones which reduces the risks associated with osteoporosis, there are apparent degradative side effects directly related to juvenile-onset osteoporosis as decreased bone development. Additionally, other mutations within this gene affected serotonin synthesis, increased bone fractures, bone pain, and impaired mobility. The function of biological systems does not exist “in a bubble” as a single isolated trait, but they cascade throughout many systems that impact-related and unrelated processes. While higher density bones have some potential benefits, side effects have rendered disorders and juvenile-onset diseases-1.
2-https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-13-26
