Department of Internal Medicine Section Endocrinology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Rare Bone Disease Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Biomolecules. 2023 Feb 2;13(2):281. doi: 10.3390/biom13020281.
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 or 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 or haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient's phenotype.
成骨不全症（OI）是一种遗传性结缔组织疾病，由于负责合成 I 型胶原的基因发生致病性变异，导致骨骼脆弱。为了对 OI 的高度临床变异性进行分类，人们努力将其分类为 Sillence 分类。然而，这种分类仅部分考虑了骨骼外表现和高度遗传变异性。目前对于遗传变异与表型之间的关系知之甚少。本研究的目的是根据 675 名荷兰 OI 患者的致病变异类型，对他们进行临床相关的遗传分层，并概述他们各自的医疗需求。从阿姆斯特丹 UMC 基因组数据库中提取了 675 名 OI 患者的临床记录，并与荷兰统计局（CBS）的记录相匹配。根据患者携带的致病性变异对其进行分类。比较了变异组之间的住院、门诊就诊、药物和诊断治疗组合（DTC）的信息。与普通荷兰人群相比，荷兰的 OI 患者似乎需要更多的 DTC、门诊就诊和住院治疗。此外，与普通人群相比，OI 患者的药物使用似乎更高。与其他组相比，具有 或 显性负性错义非甘氨酸取代的患者的医疗需求似乎较低，甚至低于 或 杂合不足的患者。在对患者的表型进行分类时，除了 Sillence 分类之外，还包括变异类型将是有用的。
