Identification of 8 new mutations in Brazilian families with Marfan syndrome

✍ Scribed by Ana B.A. Perez; Lygia V. Pereira; Decio Brunoni; Mayana Zatz; Maria Rita Passos-Bueno

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 25 KB
• Volume: 13
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(1999)13:1<84::aid-humu15>3.0.co;2-u

✦ Synopsis

Marfan Syndrome (MFS) is a connective tissue disease caused by mutations in the fibrillin-1 (FBN1) gene. Screening for mutations in all the 65 exons of the FBN1 gene in 34 unrelated patients were performed to compare the efficiency of SSCP versus Heteroduplex analysis and to verify if the spectrum of mutations in Brazilian patients is similar to the one previously reported. Fourteen different band shifts were detected by SSCP analysis; among these only 6 were also detected through Heteroduplex analysis, suggesting that SSCP analysis was a more efficient method. Except for one, the molecular alteration was confirmed in the remaining 13 cases by sequencing; five of them were neutral polymorphisms and the eight others are new pathogenic mutations, as follows: 5 missense, one nonsense and two deletions leading to a premature termination codon (PTC). All of them are located in EGF-like-calcium binding motifs (EGF-like-cb). Our findings reinforce that cysteine substitutions and PTC mutations in the region between exons 24-32 are more likely not to be associated with the neonatal phenotypes.