Novel Heterozygous Mutations Identified in Chinese Families with Marfan Syndrome.

OBJECTIVE

To detect the mutations in the fibronectin-1 gene () of four Chinese families with autosomal dominant Marfan syndrome (MFS), and to discuss the associated phenotypes.

METHODS

We examined ten patients, and five non-carriers, in four Chinese families with autosomal dominant Marfan syndrome (MFS) for mutations. Comprehensive physical, ophthalmic, and cardiovascular examinations were performed on the family members. The gene was amplified with PCR from the DNA of the patients and their relatives. The amplified products were sequenced and compared with a reference sequence from the GenBank database. The changes in the structure and function of the protein caused by the amino acid substitution were investigated with a bioinformatics analysis.

RESULTS

In our study, sequencing revealed three novel mutations, and one mutation which was found earlier in 2012. One of the novel mutations is c.649T>C in exon 7, which results in the substitution tryptophan by arginine at codon 217 (p.Trp217Arg), the other is a splice defect in intron 39 (c.4816+1G>A), and the third one is c.407G>T in exon 5, which altered an amino acid at residue 136 from Cysteine to Phenylalanine (p.Cys136Phe). The recurrent mutation was c.4151T>C in exon 34, resulting in methionine being replaced by threonine (p.Met1384Thr). The occurrence of the mutations correlated strongly with the phenotypes of the patients, and no mutation was detected in the normal relatives of the affected patients.

CONCLUSIONS

In this study, three novel and a recurrent mutations were detected. The results expand the mutation spectrum of , helping in the study of molecular pathogenesis of MFS and Marfan-related disorders.