Abstract: Objective To screen the genetic mutations in FBN1 and ADAMTSL4 genes from three families who had congenital lens subluxation by targeted gene capture with high-throughput and Sanger sequencing techniques.Methods Peripheral blood samples were collected from 14 lens subluxation patients and 3 healthy members of three families and genomic DNA was isolated. FBN1 was selected by a gene capture strategy with 65 exon capture probes. The enrichment libraries were sequenced on HiSeq2000 sequencer to determine the mutation frequency in FBN1. Probable mutations were verified by Sanger sequencing method. At the same time, ADAMTSL4 gene from three probands was also analyzed by Sanger method.Results Three different hybrid missense mutations were found in FBN1 gene from the three families. Four single nucleotide polymorphism changes were found in ADAMTSL4 gene.Conclusion FBN1 gene is the pathogenic gene that cause congenital lens subluxation in the selected three families. FBN1 genetic mutations are the primary causes leading to the clinical signs of lens subluxation.

Key words: Lens subluxation family, Targeted gene capture, High-throughput genetic sequencing method, FBN1 gene, ADAMTSL4 gene, mutation