Identification of a novel mutation of the FBN1 gene in a Chinese family with inherited ectopia lentis

Objective To identify a potential disease-causing mutation in the FBN1 gene in a Chinese family with ectopia lentis (EL). Methods Case series study. Complete physical, ophthalmic and cardiovascular examinations of all family members were conducted. Peripheral blood samples were collected from the proband and his family members with informed consents. Genomic DNAs were isolated from peripheral blood leukocytes. All 65 exons and exon-intron boundaries of the FBN1 gene were amplified by polymerase chain reaction (PCR). After purification, the PCR products were bidirectionally sequenced. Results All 3 ectopia lentis individuals were found to carry a novel missense mutation of c.1999T>C (p.Cys 515Arg) in FBN1 that is predicted to be harmful by the SIFT and Polyphen-2, while normal members of the family did not have this mutation. Furthermore, subject Ⅱ-2 and Ⅲ-1 did not show detectable abnormalities in the cardiovascular system compared to Ⅰ-2, who had ascending aorta dilation. Conclusion The EL family patients with the c.1999T>C (p.Cys 515Arg) mutation in the FBN1 gene showed different cardiovascular presentation. However, whether the younger mutation carriers of the family will evolve towards Marfan's syndrome with aging needs long-term observation. Key words: Lens subluxation; FBN1 gene; Marfan syndrome; Phenotype