Allelic heterogeneity has been demonstrated in several nuclear DNA loci, and could be divided into two subtypes: (A) One gene, one mutation, many phenotypes: For example, the C376T mutation within the LGR4 (Leucine-rich repeat-containing G-protein coupled receptor 4 gene) is strongly associated with low bone mineral density (BMD), osteoporotic fractures, as well as with an increased risk to develop squamous skin cell carcinoma and biliary tract cancer52. The gene discussed is LGR4; the disease is skin squamous cell carcinoma.