Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort

Abstract Aims 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. Methods Pat...

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Main Authors: Yan Liu, Yang Sun, Qiuyi Huo, Linghao Song, Xinyue Wang, Xin Shen, Ye Zhao, Tianhui Chen, Yongxiang Jiang
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Human Genomics
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Online Access:https://doi.org/10.1186/s40246-025-00729-6
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author Yan Liu
Yang Sun
Qiuyi Huo
Linghao Song
Xinyue Wang
Xin Shen
Ye Zhao
Tianhui Chen
Yongxiang Jiang
author_facet Yan Liu
Yang Sun
Qiuyi Huo
Linghao Song
Xinyue Wang
Xin Shen
Ye Zhao
Tianhui Chen
Yongxiang Jiang
author_sort Yan Liu
collection DOAJ
description Abstract Aims 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. Methods 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. Results 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. Conclusion 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.
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spelling doaj-art-e23c262a9c404555b9f9e195fd168a0a2025-08-20T02:01:38ZengBMCHuman Genomics1479-73642025-03-0119111310.1186/s40246-025-00729-6Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohortYan Liu0Yang Sun1Qiuyi Huo2Linghao Song3Xinyue Wang4Xin Shen5Ye Zhao6Tianhui Chen7Yongxiang Jiang8Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityAbstract Aims 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s40246-025-00729-6MicrospherophakiaGenotype-phenotype correlationGenetic landscapeOcular biometric parameters
spellingShingle Yan Liu
Yang Sun
Qiuyi Huo
Linghao Song
Xinyue Wang
Xin Shen
Ye Zhao
Tianhui Chen
Yongxiang Jiang
Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort
Human Genomics
Microspherophakia
Genotype-phenotype correlation
Genetic landscape
Ocular biometric parameters
title Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort
title_full Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort
title_fullStr Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort
title_full_unstemmed Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort
title_short Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort
title_sort genetic landscape and ocular biometric correlations in microspherophakia insights from a comprehensive patient cohort
topic Microspherophakia
Genotype-phenotype correlation
Genetic landscape
Ocular biometric parameters
url https://doi.org/10.1186/s40246-025-00729-6
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