OSTM1 pleiotropic roles from osteopetrosis to neurodegeneration.

ABSTRACT

Autosomal recessive osteopetroses (ARO) are rare genetic skeletal disorders of high clinical and molecular heterogeneity with an estimated frequency of 1250,000 worldwide. The manifestations are diverse and although individually rare, the various forms contribute to the prevalence of a significant number of affected individuals with considerable morbidity and mortality. Among the ARO classification, the most severe form is the autosomal recessive-5 (OPTB5) osteopetrosis (OMIM 259720) that results from homozygous mutation in the OSTM1 gene (607649). OSTM1 mutations account for approximately 5 % of instances of autosomal recessive osteopetrosis and lead to a highly debilitating form of the disease in infancy and death within the first few years of life (Sobacchi et al., 2013) [1].