AimsTo identify the mutation spectrum and genotype–phenotype correlations of fibrillin-1 (FBN1) mutations in a Chinese cohort with congenital ectopia lentis (EL).MethodsPatients 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.ResultsA 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).ConclusionsThis 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.

Purpose:To evaluate the clinical characteristics and ocular features of patients with acute secondary angle closure, associated with lens subluxation (ASAC-LS).Methods:We performed a retrospective study at the EENT Hospital of Fudan University, Shanghai, China. A total of 41 affected eyes from 41 patients were enrolled in this study. Furthermore, 20 affected eyes were part of the ASAC-LS cohort and 21 affected eyes were included in the acute primary angle closure (APAC) cohort. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), axial length (AL), minimum corneal curvature (K1), maximum corneal curvature (K2), and anterior chamber depth (ACD) were measured and compared between the 2 cohorts. In addition, inter-eye (intraindividual) comparison was performed.Results:The ASAC-LS cohort exhibited younger ages, more frequent trauma history (35%), lower IOP (27.43 ± 13.86 mmHg vs. 41.27 ± 10.36 mmHg), longer AL (23.96 ± 2.60 vs. 22.49 ± 0.77 mm), shallower ACD (1.28 ± 0.38 vs. 1.58 ± 0.23 mm), and bigger ACD differences (0.99 ± 0.52 vs. 0.15 ± 0.19 mm), as compared with the APAC cohort (all p < 0.05). Moreover, eyes from the lens subluxation cohort experienced worse BCVA, higher IOP, and shallower ACD than their matched unaffected eyes (all p < 0.05). Although longer AL, shallower ACD, and bigger ACD differences were strongly correlated with lens subluxation in a univariate logistic regression analysis, only the ACD difference remained significant in the multivariate model (p = 0.004, OR = 1,510.50). Additionally, according to the receiver operating characteristic (ROC) curve analysis, both ACD and ACD differences had greater value in the differential diagnosis of ASAC-LS and APAC, with a cut-off value of 1.4 and 0.63 mm, respectively.Conclusions:Shallower ACD and larger ACD differences provide the promising diagnostic potential for patients with ASAC-LS.