Novel p.G1344E mutation in <i>FBN1</i> is associated with ectopia lentis.

Abstract

Ectopia lentis refers to dislocation or subluxation of the crystalline lens. Fibrillin-1, encoded by <i>FBN1</i>, is an important microfibrillar structural component that is specifically required for the suspensory ligament of the lens. <i>FBN1</i> mutations may cause abnormal structure of microfibrils and has been associated with a broad spectrum of clinical phenotypes. In this study, we characterised a Chinese dominant family with late-onset isolated ectopia lentis caused by a novel missense <i>FBN1</i> mutation. Eight family members, including four patients with suspected isolated ectopia lentis, were recruited from Shanghai. Clinical data and family history of the proband and other affected family members were collected. Ophthalmic examination, systemic examination and echocardiography were performed. Whole exome sequencing and Sanger sequencing were used to detect potential pathogenic variants. A novel heterozygous missense mutation c.4031 G>A/p.Gly1344Glu in exon 33 of <i>FBN1</i> was identified. This mutation was detected in all affected family members and led to specific ocular system phenotypes (ectopia lentis, microspherophakia and secondary glaucoma) with minor skeletal involvement (hallux valgus). The novel c.4031G>A mutation in <i>FBN1</i> is a likely pathogenic mutation for isolated ectopia lentis. Our study expands the spectrum of <i>FBN1</i> mutations and contributes to better comprehension of genotype-phenotype correlations of ectopia lentis disease.