Identification of two novel large deletions in FBN1 gene by next-generation sequencing and multiplex ligation-dependent probe amplification

Abstract

Abstract Background Mutations in fibrillin 1 (FBN1) are known to be associated with Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Most FBN1 mutations are missense or nonsense mutations. Conventional molecular genetic testing of FBN1 using techniques such as Sanger sequencing may miss disease-causing mutations in promoter regions or other noncoding sequences as well as partial or complete gene deletions and duplications. Methods Two MFS patients referred for genetic testing were recruited and underwent next-generation sequencing, multiplex ligation-dependent probe amplification and gap PCR to identify the causative mutation. Results We identified two large genomic deletions in FBN1 from two MFS patients. One patient had a 0.23 Mb deletion spanning FBN1 exons 1–6 and the neighboring upstream gene CEP152. The other patient harbored a 1,416 bp deletion of FBN1 exon 66. Conclusion Our report expanded the number of large FBN1 deletions and highlighted the importance of screening for large deletions in FBN1 in clinical genetic testing,especially for those with classic Marfan phenotype.