{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:35:44Z","timestamp":1790847344048,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient\u2019s phenotype.<\/jats:p>","DOI":"10.3390\/biom13020281","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T04:55:12Z","timestamp":1675313712000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-3775","authenticated-orcid":false,"given":"Silvia","family":"Storoni","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Section Endocrinology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-6789","authenticated-orcid":false,"given":"Sara J. E.","family":"Verdonk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Section Endocrinology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-0402","authenticated-orcid":false,"given":"Lidiia","family":"Zhytnik","sequence":"additional","affiliation":[{"name":"Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Traumatology and Orthopeadics, University of Tartu, L. Puusepa 8, 50406 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-7115","authenticated-orcid":false,"given":"Gerard","family":"Pals","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Treurniet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Section Endocrinology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariet W.","family":"Elting","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph J. B.","family":"Sakkers","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost G.","family":"van den Aardweg","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Amsterdam University Medical Center, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-676X","authenticated-orcid":false,"given":"Elisabeth M. W.","family":"Eekhoff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Section Endocrinology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Micha","sequence":"additional","affiliation":[{"name":"Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Human Genetics, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat. 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