A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal dominant Marfan syndrome.
Genet Mol Res
; 14(2): 4125-32, 2015 Apr 27.
Article
em En
| MEDLINE
| ID: mdl-25966184
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ectopia do Cristalino
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Povo Asiático
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Fibrilina-1
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Síndrome de Marfan
Limite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Genet Mol Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China