Study On Mutations Of FBN1 And TGFBR2 Genes In Marfan Syndrome

Objective To study mutations in the fibrillin-1(FBN1) gene and Transforming Growth Factor Beta Receptor Typeâ…¡(TGFBR2)gene from 14 patients with Marfan syndrome (MFS) and identify the positions and types of these mutations. To observe the relationship between the clinical phenotypes and mutational types of FBN1 and TGFBR2 genes in Marfan patients.Methods Denaturing high-performance liquid chromatography (DHPLC) was introduced to screen for FBN1 and TGFBR2 mutations exon-by-exon. The DNA amplification fragments which DHPLC elution profiles showed different from the corresponding normal elution profile were sequenced to identify the position and types of mutations. Restriction fragment length polymorphism(RELP)was employed to further prove the mutations when needed.Results (1) DHPLC elution profile for PCR product of exon64 of FBN1 from one patient (No.14) was different from normal elution profiles. Direct sequencing showed a nonsense mutation(G2694stop) in exon64 at nucleotide 8080(8080 C>T).The nonsense mutation resulted in premature termination codon (PTC) and caused the affected FBN1 176 amino acids shorter than normal Fib-1. The nonsense mutation was further confirmed by RFLP.(2) DHPLC elution profile for PCR product of exon 29 of FBN1 from one patient (No.11) was different from normal elution profiles. Direct sequencing showed a single nucleotide...