Key result
Mutation scanning using dHPLC in 262 patients with Marfan syndrome or Marfan-like phenotypes detected 103 mutations (39.3%), of which 72 were novel.
Why the study?
Does dHPLC provide an effective method for detecting FBN1 mutations in patients with Marfan syndrome or Marfan-like phenotypes?
Observational (n=262)
Does dHPLC provide an effective method for detecting FBN1 mutations in patients with Marfan syndrome or Marfan-like phenotypes?
dHPLC is a viable, high-throughput method for detecting FBN1 mutations in patients with Marfan syndrome, identifying a high proportion of novel mutations.
May streamline FBN1 screening in suspected Marfan syndrome; leaves open prospective validation of sensitivity before routine use.
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the fibrillin-1 gene FBN1. Mutation detection of this 65-exon gene presents a particular challenge for the diagnostic service in cost, time constraints, and the need to maintain a stringently optimized assay procedure. Using denaturing high-performance liquid chromatography (dHPLC), we have designed a procedure for rapid mutation scanning, redesigning 50% of published primer sets, screening by Ensembl to avoid inclusion of polymorphic variations and employing a limited set of PCR conditions to allow for a high-throughput 96-well format. We have screened 262 unrelated patients with MFS or Marfan-like phenotypes and detected 103 (39.3%) mutations including 93 different mutations, 72 of which are novel. The mutations include 55 missense (53.4%) 19 splice site (18.5%), 17 frameshift (16.5%), 11 nonsense (10.7%) and 1 in-frame deletion/insertion.
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Howarth et al. (2007) conducted an observational in Marfan syndrome (MFS) or Marfan-like phenotypes (n=262). denaturing high-performance liquid chromatography (dHPLC) was evaluated on Mutation detection. Mutation scanning using dHPLC in 262 patients with Marfan syndrome or Marfan-like phenotypes detected 103 mutations (39.3%), of which 72 were novel.
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