title: A novel TCIRG1 gene mutation leads to severe osteopetrosis with altered content of monocytes/macrophages in several organs.
abstract: Osteopetrosis (OP) is a clinically and genetically heterogeneous disease. Defects in the TCIRG1 gene are most frequently implicated in the osteoclast-rich form of OP. Little is known about the content and/or function of monocytes and macrophages of various organs rich in those cells in patients with OP. We report a patient with a novel TCIRG1 gene mutation that led to an osteoclast-rich OP. A bone marrow transplant failed to engraft, and the patient developed pulmonary hypertension. At autopsy he was found to have abnormal remodeling of the pulmonary vasculature and alveolar proteinosis. Alveolar macrophages were decreased. Pulmonary findings in this patient could be at least partially explained by abnormal surfactant metabolism due to depleted or defective alveolar macrophages.
authors.affiliation: Department of Pathology, Children's Hospital of Wisconsin Milwaukee, WI, USA. ggheorghe@mcw.edu
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gheorghe
authors.forename: Csaba
authors.initials: C
authors.lastname: Galambos
authors.forename: Shilpa
authors.initials: S
authors.lastname: Jain
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Krishnamurti
authors.forename: Ronald
authors.initials: R
authors.lastname: Jaffe
mesh_terms: D016026:Bone Marrow Transplantation; D017809:Fatal Outcome; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000473:pathology; D007223:Infant; D016676:Macrophages, Alveolar / Q000473:pathology*; D008297:Male; D009000:Monocytes / Q000473:pathology; D009154:Mutation; D010022:Osteopetrosis / Q000235:genetics* / Q000473:pathology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases