PT  - JOURNAL ARTICLE
AU  - Zexu Chen
AU  - Tianhui Chen
AU  - Min Zhang
AU  - Jiahui Chen
AU  - Michael Deng
AU  - Jialei Zheng
AU  - Li-Na Lan
AU  - Yongxiang Jiang
TI  - <em>Fibrillin-1</em> gene mutations in a Chinese cohort with congenital ectopia lentis: spectrum and genotype–phenotype analysis
AID  - 10.1136/bjophthalmol-2021-319084
DP  - 2021 Jul 18
TA  - British Journal of Ophthalmology
PG  - bjophthalmol-2021-319084
4099  - http://bjo.bmj.com/content/early/2021/07/18/bjophthalmol-2021-319084.short
4100  - http://bjo.bmj.com/content/early/2021/07/18/bjophthalmol-2021-319084.full
AB  - 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.Data are available in a public, open-access repository. All data relevant to the study are included in the article or uploaded as supplementary information.