Fibrillin-1 gene mutations in a Chinese cohort with congenital ectopia lentis: spectrum and genotype-phenotype analysis
Zexu Chen, Tianhui Chen, Min Zhang, Jiahui Chen, Michael Deng, Jialei Zheng, Li-Na Lan, Yongxiang Jiang, Zexu Chen, Tianhui Chen, Min Zhang, Jiahui Chen, Michael Deng, Jialei Zheng, Li-Na Lan, Yongxiang Jiang
Abstract
Aims: To identify the mutation spectrum and genotype-phenotype correlations of fibrillin-1 (FBN1) mutations in a Chinese cohort with congenital ectopia lentis (EL).
Methods: Patients clinically suspected of congenital zonulopathy were screened using panel-based next-generation sequencing followed by multiplex ligation-dependent probe amplification. All the probands were subjected to thorough ocular examinations. Molecular and clinical data were integrated in pursuit of genotype-phenotype correlation.
Results: A total of 131 probands of FBN1 mutations from unrelated families were recruited. Around 65% of the probands were children younger than 9 years old. Overall, 110 distinct FBN1 mutations were identified, including 39 novel ones. The most at-risk regions were exons 13, 2, 6, 15, 24 and 33 in descending order of mutation frequency. The most prevalent mutation was c.184C>T (seven, 5.34%) in the coding sequence and c.5788+5G>A (three, 2.29%) in introns. Missense mutations were the most frequent type (103, 78.63%); half of which were distributed in the N-terminal regions (53, 51.46%). The majority of missense mutations were detected in one of the calcium-binding epidermal growth factor-like domains (62, 60.19%), and 39 (62.90%) of them were substitutions of conserved cysteine residues. Microspherophakia (MSP) was found in 15 patients (11.45%). Mutations in the middle region (exons 22-42), especially exon 26, had higher risks of combined MSP (OR, 5.51 (95% CI 1.364 to 22.274), p=0.017).
Conclusions: This study extended the knowledge of the FBN1 mutation spectrum and provided novel insights into its clinical correlation regarding EL and MSP in the Chinese population.
Keywords: genetics; lens and zonules.
Conflict of interest statement
Competing interests: None declared.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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