Liu Yan, Sun Yang, Huo Qiuyi, Song Linghao, Wang Xinyue, Shen Xin, Zhao Ye, Chen Tianhui, Jiang Yongxiang
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
Key Laboratory of Myopia Key laboratory of Myopia and Related Eye Diseases, NHC; Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China.
Hum Genomics. 2025 Mar 1;19(1):22. doi: 10.1186/s40246-025-00729-6.
The aim of this study is to elucidate the genetic landscape of microspherophakia (MSP) and describe the genotype-phenotype correlation of MSP. Additionally, the study seeks to enhance the understanding of the pathogenic mechanisms of MSP through the discovery of novel loci.
Patients diagnosed with MSP at the Eye and ENT Hospital of Fudan University, Shanghai, were included in the study and all underwent panel-based next-generation sequencing and bioinformatics analysis. Comprehensive ophthalmologic evaluations were conducted for each participant.
Our analysis encompassed 118 eyes from 59 patients with MSP, revealing 13 gene variations linked to the condition. Notably, FBN1 mutations were identified in 31 patients (52.5%), highlighting its higher prevalence. Among the genetic variations discovered, 28 represented novel mutations. Statistical analysis unveiled significant associations between specific gene mutations and ocular biometric parameters: axial length (AL, p = 0.011), Z-score axial length (Z-AL, p < 0.001), white-to-white (WTW, p = 0.009), Z-score white-to-white (p = 0.012), mean keratometry (p < 0.001), astigmatism (AST, p = 0.021), anterior chamber depth (ACD, p = 0.003), lens thickness (LT, p = 0.012) and central endothelial cell count/mm2 (p = 0.005). Patients with FBN1 mutations had the longest AL, while those with CBS mutations showed significantly wilder WTW measurements. Patients with ADAMTS17 mutations presented with increased LT and decreased WTW, ADAMTSL4 mutations were linked to the greater Km and AST. Patients with LTBP mutations exhibited the largest WTW, and ASPH mutations was associated with the shortest AL but thick LT. Additionally, there was a relationship among gene mutations, diagnostic age and ocular biometric parameters.
The study demonstrates that MSP is associated with a diverse range of genetic mutations, with FBN1 being the most common. Novel mutations were identified, and significant correlations were found between specific genetic variations and ocular biometric parameters. These results provide new insights into the genetic underpinnings of MSP and its clinical characteristics, advancing our understanding of the condition's pathogenic mechanisms.
本研究旨在阐明小眼球症（MSP）的遗传图谱，并描述MSP的基因型-表型相关性。此外，该研究旨在通过发现新的基因座来加深对MSP致病机制的理解。
纳入在上海复旦大学附属眼耳鼻喉科医院被诊断为MSP的患者，所有患者均接受基于基因panel的二代测序和生物信息学分析。对每位参与者进行全面的眼科评估。
我们的分析涵盖了59例MSP患者的118只眼睛，发现了13个与该疾病相关的基因变异。值得注意的是，在31例患者（52.5%）中鉴定出FBN1突变，突出了其较高的患病率。在发现的基因变异中，28个代表新突变。统计分析揭示了特定基因突变与眼部生物测量参数之间的显著关联：眼轴长度（AL，p = 0.011）、眼轴长度Z值（Z-AL，p < 0.001）、白对白距离（WTW，p = 0.009）、白对白距离Z值（p = 0.012）、平均角膜曲率（p < 0.001）、散光（AST，p = 0.021）、前房深度（ACD，p = 0.003）、晶状体厚度（LT，p = 0.012）和中央内皮细胞计数/mm²（p = 0.005）。携带FBN1突变的患者AL最长，而携带CBS突变的患者WTW测量值明显更宽。携带ADAMTS17突变的患者LT增加而WTW减少，ADAMTSL4突变与更大的Km和AST相关。携带LTBP突变的患者WTW最大，而携带ASPH突变的患者AL最短但LT厚。此外，基因突变、诊断年龄和眼部生物测量参数之间存在关系。
该研究表明MSP与多种基因突变相关，其中FBN1最为常见。鉴定出了新突变，并发现特定基因变异与眼部生物测量参数之间存在显著相关性。这些结果为MSP的遗传基础及其临床特征提供了新的见解，推进了我们对该疾病致病机制的理解。
