{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:31:50Z","timestamp":1790688710803,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Children's Hospital Charity, Sheffield, Research Fund","award":["CA11004"],"award-info":[{"award-number":["CA11004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Osteogenesis Imperfecta (OI) is an inherited bone fragility disorder most commonly associated with autosomal dominant mutations in the type I collagen genes. Autosomal recessive mutations in a number of genes have also been described, including the <jats:italic>BMP1<\/jats:italic> gene that encodes the mammalian Tolloid (mTLD) and its shorter isoform bone morphogenic protein\u20101 (BMP1). To date, less than 20 individuals with OI have been identified with <jats:italic>BMP1<\/jats:italic> mutations, with skeletal phenotypes ranging from mild to severe and progressively deforming. In the majority of patients, bone fragility was associated with increased bone mineral density (BMD); however, the full range of phenotypes associated with <jats:italic>BMP1<\/jats:italic> remains unclear. Here, we describe three children with mutations in <jats:italic>BMP1<\/jats:italic> associated with a highly variable phenotype: a sibship homozygous for the c.2188delC mutation that affects only the shorter BMP1 isoform and a further patient who is compound heterozygous for a c.1293C&gt;G nonsense mutation and a c.1148G&gt;A missense mutation in the CUB1 domain. These individuals had recurrent fractures from early childhood, are hypermobile and have no evidence of dentinogenesis imperfecta. The homozygous siblings with OI had normal areal BMD by dual energy X\u2010ray absorptiometry whereas the third patient presented with a high bone mass phenotype. Intravenous bisphosphonate therapy was started in all patients, but discontinued in two patients and reduced in another due to concerns about increasing bone stiffness leading to chalk\u2010stick fractures. Given the association of <jats:italic>BMP1<\/jats:italic>\u2010related OI with very high bone material density, concerns remain whether anti\u2010resorptive therapy is indicated in this ultra\u2010rare form of OI.\u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37958","type":"journal-article","created":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T06:07:01Z","timestamp":1472623621000},"page":"3150-3156","source":"Crossref","is-referenced-by-count":38,"title":["Phenotypic variability in patients with osteogenesis imperfecta caused by <i>BMP1<\/i> mutations"],"prefix":"10.1002","volume":"170","author":[{"given":"Rebecca C.","family":"Pollitt","sequence":"first","affiliation":[{"name":"Sheffield Diagnostic Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK"},{"name":"Academic Unit of Child Health Department of Oncology and Metabolism University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vrinda","family":"Saraff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Dalton","sequence":"additional","affiliation":[{"name":"Sheffield Diagnostic Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma A.","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital Birmingham UK"},{"name":"Institute of Metabolism and Systems Research University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick J.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital Birmingham UK"},{"name":"Institute of Metabolism and Systems Research University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda J.","family":"Sobey","sequence":"additional","affiliation":[{"name":"National EDS Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Zulf","family":"Mughal","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Royal Manchester Children's Hospital Central Manchester University Hospitals Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Hobson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Chapel Allerton Hospital Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Paediatric Orthopaedic Surgery Royal Manchester Children's Hospital Central Manchester University Hospitals NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Bishop","sequence":"additional","affiliation":[{"name":"Academic Unit of Child Health Department of Oncology and Metabolism University of Sheffield Sheffield UK"},{"name":"Department of Paediatric Endocrinology Royal Manchester Children's Hospital Central Manchester University Hospitals Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Arundel","sequence":"additional","affiliation":[{"name":"Highly Specialised Severe Complex and Atypical OI Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"H\u00f6gler","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital Birmingham UK"},{"name":"Institute of Metabolism and Systems Research University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Highly Specialised Severe Complex and Atypical OI Service Sheffield Children's NHS Foundation Trust Sheffield UK"},{"name":"Sheffield Clinical Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.026"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-009-0899-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2014.01.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9799-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.10.010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21475"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21647"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.021"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2008.11.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16051-0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1998"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2473"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36427"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2805"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.02.071"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa023110"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37958","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37958","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T01:40:55Z","timestamp":1696642855000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,30]]},"references-count":17,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1002\/ajmg.a.37958"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37958","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,30]]}}}