To explore if mutations in FBN3 have some relation with MFS, we analyzed FBN3 allelic variants in twelve Chinese patients with MFS by direct sequencing analysis.
We identified six single nucleotide polymorphisms (SNPs) that have already been reported for FBN3 and five novel mutations including two frameshift mutations (c.3648delC and c.3686insC) and three missense mutations (p.454T greater than P, p.1642G greater than P and p.1876G greater than C).
These novel mutations were found in FBN3 of MFS patients only while forty healthy individuals showed none of the mutations indicating that these mutations might be the cause for MFS.
The fibrillin-3 (FBN3) gene exists on human chromosome 19p13 and shows high homology to other fibrillin family members (Nagase et al., 2001).
We amplified exons 11, 22, 25, 30, 38 and 44 of FBN3 by polymerase chain reaction (PCR) using the primer sequences given in Table 1.
We sequenced exons 11, 22, 25, 38 and 44 in patients and in normal individuals, aligning the sequences from these individuals with standard FBN3 sequence showed different polymorphisms (Table III).
Two new frameshift mutations in exon 25 of FBN3 were also identified.
Table I.- List of primers for amplification and sequencing of FBN3 gene.
We screened FBN3 for c.3686insC in all the family members of the patients and found that all the patients in this family harbored the insertion that was not found in the normal members of the family.
FBN3 is important extracellular matrix macromolecules that perform architectural functions in most connective tissues as FBN1, and it has been proved a cause of Weill- Marchesani syndrome that is caused by the disruption of extracellular matrix macromolecules (Robinson and Godfrey, 2000).
As these SNPs were found in FBN3 of both patients and normal controls, so they may not be responsible for MFS (Uyeda et al., 2004).