title: Severe malignant osteopetrosis caused by a GL gene mutation.
abstract: Infantile malignant autosomal recessive osteopetrosis is a genetically heterogeneous disease caused by the inability of OCLs to resorb and remodel bone, resulting in generalized osteosclerosis and obliteration of marrow spaces and cranial foramina. The classical clinical features are pathological fractures, visual impairment, and bone marrow failure. Two human genes have been described as the cause of this form of osteopetrosis: the T-cell immune-regulator-1 (TCIRG1) gene, which is mutated in >50% of the patients, and the chloride channel 7 (ClCN7) gene, which accounts for approximately 10% of cases. We report the clinical, radiographic, and histopathologic findings of the first human osteopetrosis case caused by a mutation in the grey-lethal (GL) gene. The patient, a 9-day-old male infant, presented with a very severe osteopetrotic phenotype including substantial hepatosplenomegaly since birth, cytopenia, and progressive major liver failure. Skeletal radiographs revealed a generalized increase in bone density with loss of corticomedullary differentiation. Histopathologic bone examination showed the typical osteopetrotic changes, with absence of resorptive activity, and osteoclasts, slightly decreased in number, with evident morphological alterations.
authors.affiliation: Dipartimento di Scienze Pediatriche, Università di Torino, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Quarello
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.forename: Laura
authors.initials: L
authors.lastname: Barberis
authors.forename: Claudio
authors.initials: C
authors.lastname: Defilippi
authors.forename: M Francesca
authors.initials: MF
authors.lastname: Campagnoli
authors.forename: Leandra
authors.initials: L
authors.lastname: Silvestro
authors.forename: Annalisa
authors.initials: A
authors.lastname: Frattini
authors.forename: Nader
authors.initials: N
authors.lastname: Chalhoub
authors.forename: Jean
authors.initials: J
authors.lastname: Vacher
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
mesh_terms: D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D001921:Brain / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D011859:Radiography; D044767:Ubiquitin-Protein Ligases
chemical_list: D008565:Membrane Proteins; C489946:OSTM1 protein, human; D044767:Ubiquitin-Protein Ligases