Abstract:  Objective  To describe the genetic and clinical characteristics of a cohort of Chinese patients with FBN1 variants and to explore genotype-phenotype correlations in ocular manifestations. Design Retrospective case series. Participants 36 patients from 24 unrelated families who carried variants in FBN1. Methods Detailed ophthalmic/systemic evaluations were performed on the patients. Peripheral venous blood was collected from family members. Sanger sequencing was employed for validation and family co-segregation analysis to identify pathogenic variant sites. Main Outcome Measures Pathogenic gene variants, ocular clinical manifestations, and systemic manifestations. Results 23 variants in FBN1 were identified; seven variants were novel. The variants included 21 (91.3%) missense variants, one in-frame deletion, and one large novel deletion encompassing exon 47-54. The patients showed clinical diversity, ranging from typical Marfan syndrome to isolated ectopia lentis (EL) and Weill Marchesani syndrome. All patients with cysteine-erasing missense variants suffered from EL and high myopia, and approximately 30% occurred retinal detachment(RD). Conversely, patients with cysteine-forming variants exhibited a higher prevalence and severity of astigmatism. A patient with compound-heterozygous missense variants exhibited severe ocular and cardiovascular manifestations. Conclusions Our results expanded the pathogenic variant spectrum of FBN1. We observed that patients with cysteine-erasing missense variants were at a high risk of RD. These findings will provide some basis for genetic counselling and preventive treatment of RD risk.

Key words: Marfan syndrome, FBN1 , gene, Ectopia lentis, Phenotype, Gene variation