{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:37:43Z","timestamp":1775093863839,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2004,7,1]],"date-time":"2004-07-01T00:00:00Z","timestamp":1088640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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 &amp;gt;50% of the patients, and the chloride channel 7 (ClCN7) gene, which accounts for \u223c10% 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.<\/jats:p>","DOI":"10.1359\/jbmr.040407","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T00:24:04Z","timestamp":1146097444000},"page":"1194-1199","source":"Crossref","is-referenced-by-count":51,"title":["Severe Malignant Osteopetrosis Caused by a <i>GL<\/i> Gene Mutation"],"prefix":"10.1093","volume":"19","author":[{"given":"Paola","family":"Quarello","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Universit\u00e0 di Torino, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Forni","sequence":"additional","affiliation":[{"name":"Sezione di Anatomia Patologica, Ospedale Infantile Regina Margherita, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Barberis","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Universit\u00e0 di Torino, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Defilippi","sequence":"additional","affiliation":[{"name":"Sezione di Anatomia Patologica, Ospedale Infantile Regina Margherita, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Francesca","family":"Campagnoli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Universit\u00e0 di Torino, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandra","family":"Silvestro","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Universit\u00e0 di Torino, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Frattini","sequence":"additional","affiliation":[{"name":"Istituto di Tecnologie Biomediche, CNR, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nader","family":"Chalhoub","sequence":"additional","affiliation":[{"name":"Section of Cellular Interactions and Development, Clinical Research Institute of Montreal, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Vacher","sequence":"additional","affiliation":[{"name":"Section of Cellular Interactions and Development, Clinical Research Institute of Montreal, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo","family":"Ramenghi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Universit\u00e0 di Torino, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019200521900_bib1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1542\/peds.93.2.247","article-title":"Autosomal recessive osteopetrosis: Variability of findings at diagnosis and during the natural course","volume":"93","author":"Gerristen","year":"1994","journal-title":"Pediatrics"},{"key":"2024013019200521900_bib2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0022-3476(77)80441-1","article-title":"Osteopetrosis in children: A report of 26 cases","volume":"91","author":"Loria-Cortes","year":"1977","journal-title":"J Pediatr"},{"key":"2024013019200521900_bib3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0022-3476(05)82557-0","article-title":"Recombinant human interferon gamma therapy for osteopetrosis","volume":"121","author":"Key","year":"1992","journal-title":"J Pediatr"},{"key":"2024013019200521900_bib4","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0022-3476(05)82004-9","article-title":"Bone marrow transplantation for osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group","volume":"125","author":"Gerristen","year":"1994","journal-title":"J Pediatr"},{"key":"2024013019200521900_bib5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/adc.80.3.273","article-title":"Importance of neurological assessment before bone marrow transplantation for osteopetrosis","volume":"80","author":"Abinum","year":"1999","journal-title":"Arch Dis Child"},{"key":"2024013019200521900_bib6","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s002470100008","article-title":"Imaging of infantile osteopetrosis before and after bone marrow transplantation","volume":"31","author":"Cheow","year":"2001","journal-title":"Pediatr Radiol"},{"key":"2024013019200521900_bib7","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/sj.bmt.1704194","article-title":"Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: An EBMT report","volume":"32","author":"Driessen","year":"2003","journal-title":"Bone Marrow Transplant"},{"key":"2024013019200521900_bib8","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1136\/adc.83.5.449","article-title":"Autosomal recessive osteopetrosis: Diagnosis, management, and outcome","volume":"83","author":"Wilson","year":"2000","journal-title":"Arch Dis Child"},{"key":"2024013019200521900_bib9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/77131","article-title":"Defects in the TCIRG1-encoded 116 kD subunit of the vacuolar proton pump are responsible for a subset of autosomal recessive osteopetrosis","volume":"25","author":"Frattini","year":"2000","journal-title":"Nat Genet"},{"key":"2024013019200521900_bib10","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/hmg\/9.13.2059","article-title":"Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis","volume":"9","author":"Kornak","year":"2000","journal-title":"Hum Mol Genet"},{"key":"2024013019200521900_bib11","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1093\/hmg\/10.17.1767","article-title":"The mutational spectrum of human malignant autosomal recessive osteopetrosis","volume":"10","author":"Sobacchi","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2024013019200521900_bib12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0002-9440(10)63798-4","article-title":"Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis","volume":"162","author":"Taranta","year":"2003","journal-title":"Am J Pathol"},{"key":"2024013019200521900_bib13","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1093\/hmg\/10.25.2861","article-title":"Albers-Sch\u00f6nberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene","volume":"10","author":"Cleiren","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2024013019200521900_bib14","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1359\/jbmr.2003.18.10.1740","article-title":"Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis","volume":"18","author":"Frattini","year":"2003","journal-title":"J Bone Miner Res"},{"key":"2024013019200521900_bib15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0092-8674(01)00206-9","article-title":"Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man","volume":"104","author":"Kornak","year":"2001","journal-title":"Cell"},{"key":"2024013019200521900_bib16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S8756-3282(01)00416-1","article-title":"The mouse osteopetrotic grey-lethal mutation induces a defect in osteoclast maturation\/function","volume":"28","author":"Rajapurohitam","year":"2001","journal-title":"Bone"},{"key":"2024013019200521900_bib17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nm842","article-title":"Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and in human","volume":"9","author":"Chalhoub","year":"2003","journal-title":"Nat Med"},{"key":"2024013019200521900_bib18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1046\/j.1365-2990.2003.00474.x","article-title":"Neurological aspects of osteopetrosis","volume":"29","author":"Steward","year":"2003","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2024013019200521900_bib19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1212\/WNL.33.4.437","article-title":"Infantile osteopetrosis and neuronal storage disease","volume":"33","author":"Ambler","year":"1983","journal-title":"Neurology"},{"key":"2024013019200521900_bib20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/BF00690531","article-title":"The association of infantile osteopetrosis and neuronal storage disease in two brothers","volume":"75","author":"Jagadha","year":"1988","journal-title":"Acta Neuropathol (Berl)"},{"key":"2024013019200521900_bib21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1159\/000120923","article-title":"Association of infantile neuroaxonal dystrophy and osteopetrosis: A rare autosomal recessive disorder","volume":"22","author":"Rees","year":"1995","journal-title":"Pediatr Neurosurg"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2FJBMR.040407","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/7\/1194\/56474727\/5650190719.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/7\/1194\/56474727\/5650190719.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:06:55Z","timestamp":1710342415000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/19\/7\/1194-1199\/7592783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,1]]},"references-count":21,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2004,7,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.040407","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,7,1]]},"published":{"date-parts":[[2004,7,1]]}}}