title: A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal dominant Marfan syndrome.
abstract: The purpose of this study was to identify the clinical features and mutations in the fibrillin-1 gene (FBN1) in a large Chinese family with autosomal dominant Marfan syndrome (MFS). Seventeen members from a Chinese family of 4 generations were included in the study. All members underwent complete ophthalmic examination. Molecular genetic analysis was performed on all subjects. All exons of FBN1 were amplified by polymerase chain reaction, sequenced, and the sequences were compared with a reference database. Variations were evaluated in family members as well as 100 normal controls. Changes in structure and function of the protein induced by amino acid variation were predicted by bioinformatic analysis. Ectopia lentis, dolichostenomelia, arachnodactyly, and tall stature were present in all patients diagnosed with MFS. The novel heterozygous missense mutation c.2243 T>G (p.C781W) in exon 19 of FBN1 was identified in all 5 patients, but not in other family members or 100 normal controls. This mutation caused an amino acid substitution of cysteine to tryptophan at position 781 (p.C781W) of the FBN1 protein. This mutation occurred in a highly conserved region and may cause structural and functional changes in the protein according to our bioinformatic analysis. Our results suggest that the novel mutation C781W of FBN1 is responsible for the pathogenesis of MFS in this pedigree.
authors.affiliation: The State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
authors.forename: N
authors.initials: N
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital, University of South China, Hengyang, China.
authors.forename: D-F
authors.initials: DF
authors.lastname: Lei
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
authors.forename: S-P
authors.initials: SP
authors.lastname: Cai
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China xliu1213@126.com.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004479:Ectopia Lentis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D000071837:Fibrillins; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; C000605722:FBN1 protein, human; D054392:Adipokines