Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder due to pathogenic variants in Fibrillin-1 (FBN1) affecting nearly one in every 10,000 individuals. We report a 16-month-old female with early-onset MFS heterozygous for an 11.2 kb de novo duplication within the FBN1 gene. Tandem location of the duplication was further confirmed by optical genome mapping in addition to genetic sequencing and chromosomal microarray. This is the third reported case of a large multi-exon duplication in FBN1, and the only one confirmed to be in tandem. As the vast majority of pathogenic variants associated with MFS are point mutations, this expands the landscape of known FBN1 pathogenic variants and supports consistent use of genetic testing strategies that can detect large, indel-type variants.
Keywords: FBN1; Fibrillin-1; Marfan syndrome; optical genome mapping.
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.