title: Osteoclast morphology in autosomal recessive malignant osteopetrosis due to a TCIRG1 gene mutation.
abstract: Bone biopsies were performed before and 7 weeks after transplantation of HLA-compatible bone marrow from the sister of a 3-month-old male infant with malignant autosomal recessive osteopetrosis due to a mutation in the TCIRG1 (ATP6i) gene. The first biopsy showed broad, immature bony trabeculae and no medullary hematopoiesis. Only few osteoclasts were present and electron microscopy showed absence of ruffled borders. The post transplant biopsy revealed donor osteoclasts with ruffled borders and intracytoplasmic mineral crystals as proof of active bone resorption that had not yet been detectable radiographically. Osteopetrosis is a genetically heterogeneous disease. Definition at the DNA-level will enable comparison of treatment strategies and prenatal diagnosis. As shown in this patient, the autosomal recessive form caused by a TCIRG1 gene mutation may be amenable to bone marrow transplantation. Activity of donor osteoclasts can be demonstrated morphologically on biopsy, before bone remodeling becomes evident radiologically.
authors.affiliation: Pediatric Pathology Section, Department of Pathology, University Hospital Zurich, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bruder
authors.forename: Thomas
authors.initials: T
authors.lastname: Stallmach
authors.forename: Karin
authors.initials: K
authors.lastname: Peier
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Paolo
authors.initials: P
authors.lastname: Vezzoni
mesh_terms: D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000473:pathology; D016026:Bone Marrow Transplantation; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D010010:Osteoclasts / Q000473:pathology* / Q000648:ultrastructure; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D021122:Protein Subunits / Q000235:genetics; D014463:Ultrasonography; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
chemical_list: D021122:Protein Subunits; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases