NGS DATA for OSTEOGENESIS IMPERFECTA affected patients. OSTEOGENSIS IMPERFECTA

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes involved in collagen posttranslational modification, processing, crosslinking, as well as osteoblast differentiation and bone mineralization have also been associated with OI. In this study, we present the results of next- generation sequencing (NGS) analysis using a custom panel of 11 genes known to be associated with OI. This clinical study enrolled a total of 10 patients, comprising 7 males and 3 females from 7 families, all from the Puglia Region in South Italy, providing a detailed overview of their age, gender, family history, OI type, and non-skeletal features. The genetic analysis revealed 5 PVs in the COL1A1 gene and 2 PVs in the COL1A2 gene. Importantly, three of these PVs have not been previously reported in the literature. These include two novel heterozygous frameshift PVs in COL1A1 (c.2890_2893del and c.3887del) and one novel heterozygous missense PV in COL1A2 (c.596G>T). The identification of these previously unreported PVs expands the variant spectrum of the COL1A1 and COL1A2 genes and may have implications for accurate diagnosis, genetic counselling, and potential therapeutic interventions in affected individuals and their families.

成骨不全症（Osteogenesis imperfecta, OI）是一类具有临床与遗传异质性的骨骼系统疾病。多数受累病例由COL1A1与COL1A2基因的常染色体显性致病变异（pathogenic variants, PVs）引发，这两个基因编码Ⅰ型胶原。此外，参与胶原翻译后修饰、加工、交联过程，以及成骨细胞分化与骨矿化的其他基因的致病变异，也与OI相关。本研究采用针对11种已知与OI相关基因的定制基因检测panel，开展下一代测序（next-generation sequencing, NGS）分析，现将结果报告如下。本临床研究共纳入来自意大利南部普利亚大区7个家系的10例患者，其中男性7例、女性3例，并详细收集了所有受试者的年龄、性别、家族史、OI分型及非骨骼系统表现等临床信息。基因检测结果显示，COL1A1基因中检出5种致病变异，COL1A2基因中检出2种致病变异。尤为重要的是，其中3种致病变异此前未见文献报道，具体包括COL1A1基因的2种新发杂合移码致病变异（c.2890_2893del与c.3887del），以及COL1A2基因的1种新发杂合错义致病变异（c.596G>T）。上述未被既往报道的致病变异的发现，拓展了COL1A1与COL1A2基因的变异谱系，可为受累患者及其家属的精准诊断、遗传咨询及潜在治疗干预提供重要参考依据。