Fibrillin-1 gene mutations in a Chinese cohort with congenital ectopia lentis: spectrum and genotype–phenotype analysis. Issue 12 (19th July 2021)

• Record Type: Journal Article
• Authors: Chen, Zexu; Chen, Tianhui; Zhang, Min; Chen, Jiahui; Deng, Michael; Zheng, Jialei; Lan, Li-Na; Jiang, Yongxiang
• Is Part Of: British journal of ophthalmology. Volume 106:Issue 12(2022)
• Page Start: 1655
• Page End: 1661
• Publication Date: 2021-07-19
• Subjects: genetics -- lens and zonules; Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjophthalmol-2021-319084
• Languages: English
• ISSNs: 0007-1161

Abstract

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.