{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:26:17Z","timestamp":1790807177060,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303375\/2019\u20101 (D.R.B)"],"award-info":[{"award-number":["303375\/2019\u20101 (D.R.B)"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Osteogenesis imperfecta (OI) is a rare low\u2010bone mass skeletal Mendelian disorder characterized by bone fragility leading to bone fractures, with deformities and stunted growth in the more severe phenotypes. Other common, nonskeletal findings include blue sclerae and dentinogenesis imperfecta. It is caused mainly by quantitative or structural defects in type I collagen, although dysregulation of different signaling pathways that play a role in bone morphogenesis has been described to be associated with a small fraction of individuals with OI. Recently, a homozygous variant in the translation start site of\n                    <jats:italic>CCDC134<\/jats:italic>\n                    , showing increased activation of the RAS\/MAPK signaling pathway, has been reported in three families of Moroccan origin with a severe, deforming form of OI. We report on a 9\u2010year\u2010old Brazilian boy, harboring the same homozygous variant in\n                    <jats:italic>CCDC134<\/jats:italic>\n                    , also presenting severe bone involvement. This report contributes to the phenotypic delineation of this novel autosomal recessive form of OI, which presents with high prevalence of nonunion fractures considered rare events in OI in general. In addition, it expands the phenotype to include base skull anomalies, potentially leading to serious complications, as seen in severe forms of OI. A poor response to bisphosphonate therapy was observed in these individuals. As the variant in\n                    <jats:italic>CCDC134<\/jats:italic>\n                    leads to dysregulation of the RAS\/MAPK signaling pathway, drugs targeted to this pathway could be an alternative to achieve a better management of these individuals.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62651","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T08:14:17Z","timestamp":1641975257000},"page":"1545-1549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The recurrent homozygous translation start site variant in\n                    <scp>\n                      <i>CCDC134<\/i>\n                    <\/scp>\n                    in an individual with severe osteogenesis imperfecta of\n                    <scp>non\u2010Morrocan<\/scp>\n                    ancestry"],"prefix":"10.1002","volume":"188","author":[{"given":"Taccyanna M.","family":"Ali","sequence":"first","affiliation":[{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca D. W.","family":"Linnenkamp","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Instituto da Crian\u00e7a do Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme L.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Unidade de Gen\u00e9tica Instituto da Crian\u00e7a do Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Diagn\u00f3stico das Am\u00e9ricas SA DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-7341","authenticated-orcid":false,"given":"Rachel S.","family":"Honjo","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Instituto da Crian\u00e7a do Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamilton","family":"Cabral de Menezes Filho","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Pedi\u00e1trica Instituto da Crian\u00e7a do Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Instituto da Crian\u00e7a do Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-6777","authenticated-orcid":false,"given":"D\u00e9bora R.","family":"Bertola","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias Universidade de 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