Mutation analysis of FBN1 gene in two Chinese families with congenital ectopia lentis in northern China

• Main Authors: Su-Zhen Tang, Ya-Ning Liu, Shao-Hua Hu, Hao Chen, Hui Zhao, Xue-Mei Feng, Xiao-Jing Pan, Peng Chen
• Format: Article
• Language: English
• Published: Press of International Journal of Ophthalmology (IJO PRESS) 2019-11-01
• Series: International Journal of Ophthalmology
• Subjects: congenital ectopia lentis; autosomal dominant; targeted next-generation sequencing; fbn1; fibrillin-1
• Online Access: http://www.ijo.cn/en_publish/2019/11/20191102.pdf
• ISSN: 2222-3959; 2227-4898

AIM: To summarize the phenotypes and identify the underlying genetic cause of the fibrillin-1 (FBN1) gene responsible for congenital ectopia lentis (EL) in two Chinese families in northern China. METHODS: A detailed family history and clinical data from all participants were collected by clinical examination. The candidate genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. Haplotyping was used to confirm the mutation sequence. Real-time PCR was used to determine the FBN1 messenger ribonucleic acid (mRNA) levels in patients with EL and in unaffected family members. RESULTS: The probands and other patients in the two families were affected with congenital isolated EL. A heterozygous FBN1 mutation in exon 21 (c.2420_IVS20-8 delTCTGAAACAinsCGAAAG) was identified in FAMILY-1. A heterozygous FBN1 mutation in exon 14 (c.1633C>T, p.R545C) was identified in FAMILY-2. Each mutation co-segregated with the affected individuals in the family and did not exist in unaffected family members and 200 unrelated normal controls. CONCLUSION: The insertion-deletion mutation (c.2420 IVS20-8delTCTGAAACA insCGAAAG) in the FBN1 gene is first identified in isolated EL. The mutation (c.1633C>T) in the FBN1 gene was a known mutation in EL patient. The variable phenotypes among the patients expand the phenotypic spectrum of EL in a different ethnic background.