Severe neuronopathic autosomal recessive osteopetrosis due to homozygous deletions affecting OSTM1

on

Abstract: Autosomal recessive osteopetrosis (ARO, MIM 259700) is a genetically heterogeneous rare skeletal disorder characterized by failure of osteoclast resorption leading to pathologically increased bone density, bone marrow failure, and fractures. In the neuronopathic form neurological complications are especially severe and progressive. An early identification of the underlying genetic defect is imperative for assessment of prognosis and treatment by hematopoietic stem cell transplantation. Here we describe for the first time homozygous microdeletions of different sizes affecting the OSTM1 gene in two unrelated consanguineous families with children suffering from neuronopathic infantile malignant osteopetrosis. Patients showed an exceptionally severe phenotype with variable CNS malfor…