Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
J Endocrinol Invest. 2024 Jan;47(1):67-77. doi: 10.1007/s40618-023-02123-2. Epub 2023 Jun 4.
To evaluate the genotypic and phenotypic relationship in a large cohort of OI patients and to compare the differences between eastern and western OI cohorts.
A total of 671 OI patients were included. Pathogenic mutations were identified, phenotypic information was collected, and relationships between genotypes and phenotypes were analyzed. Literature about western OI cohorts was searched, and differences were compared between eastern and western OI cohorts.
A total of 560 OI patients were identified as carrying OI pathogenic mutations, and the positive detection rate of disease-causing gene mutations was 83.5%. Mutations in 15 OI candidate genes were identified, with COL1A1 (n = 308, 55%) and COL1A2 (n = 164, 29%) being the most common mutations, and SERPINF1 and WNT1 being the most common biallelic variants. Of the 414 probands, 48.8, 16.9, 29.2 and 5.1% had OI types I, III, IV and V, respectively. Peripheral fracture was the most common phenotype (96.6%), and femurs (34.7%) were most commonly affected. Vertebral compression fracture was observed in 43.5% of OI patients. Biallelic or COL1A2 mutation led to more bone deformities and poorer mobility than COL1A1 mutation (all P < 0.05). Glycine substitution of COL1A1 or COL1A2 or biallelic variants led to more severe phenotypes than haploinsufficiency of collagen type I α chains, which induced the mildest phenotypes. Although the gene mutation spectrum varied among countries, the fracture incidence was similar between eastern and western OI cohorts.
The findings are valuable for accurate diagnosis and treatment of OI, mechanism exploration and prognosis judgment. Genetic profiles of OI may vary among races, but the mechanism needs to be explored.
评估大量成骨不全症（OI）患者的基因型和表型关系，并比较东西方 OI 队列的差异。
共纳入 671 例 OI 患者。鉴定致病性突变，收集表型信息，并分析基因型与表型之间的关系。检索有关西方 OI 队列的文献，并比较东西方 OI 队列之间的差异。
共发现 560 例 OI 患者携带 OI 致病性突变，致病基因突变的阳性检出率为 83.5%。鉴定出 15 个 OI 候选基因的突变，COL1A1（n=308，55%）和 COL1A2（n=164，29%）突变最常见，SERPINF1 和 WNT1 最常见的双等位基因变异。在 414 名先证者中，OI 类型 I、III、IV 和 V 的比例分别为 48.8%、16.9%、29.2%和 5.1%。周围骨折是最常见的表型（96.6%），股骨（34.7%）最常受累。43.5%的 OI 患者存在椎体压缩性骨折。COL1A1 或 COL1A2 的双等位基因或突变导致比 COL1A1 突变更严重的骨骼畸形和运动能力下降（均 P<0.05）。COL1A1 或 COL1A2 的甘氨酸取代或双等位基因变异导致比 I 型胶原α链单倍不足更严重的表型，而后者导致最轻微的表型。尽管各国的基因突变谱有所不同，但东西方 OI 队列的骨折发生率相似。
这些发现对 OI 的准确诊断和治疗、机制探索和预后判断具有重要价值。OI 的遗传特征可能因种族而异，但机制仍需探索。
