title: Severe Marfan syndrome due to FBN1 exon deletions.
abstract: Marfan syndrome is an autosomal dominant condition, with manifestations mainly in the skeletal, ocular, and cardiovascular systems. The disorder is caused by mutations in fibrillin-1 gene (FBN1). The majority of these are family-specific point mutations, with a small number being predicted to cause exon-skipping. To date, there have only been five reports of in-frame exon deletions in FBN1, with the largest of these spanning three exons. Mosaicism is rarely recorded and has only been reported in the unaffected, or mildly affected, parents of probands. Here, we report on the clinical histories of two children with exon deletions in FBN1. Both have severe Marfan syndrome with significant signs in infancy. One patient has a deletion of exon 33, which has not previously been reported. The other has the largest reported deletion, which spans 37 exons, and also represents the first reported case of mosaicism in a patient with Marfan syndrome.
authors.affiliation: Wessex Clinical Genetics Service, Southampton, UK. moira.blyth@suht.swest.nhs.uk
authors.forename: Moira
authors.initials: M
authors.lastname: Blyth
authors.forename: Nicola
authors.initials: N
authors.lastname: Foulds
authors.forename: Claire
authors.initials: C
authors.lastname: Turner
authors.forename: David
authors.initials: D
authors.lastname: Bunyan
mesh_terms: D002675:Child, Preschool; D005091:Exons / Q000235:genetics*; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008382:Marfan Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008840:Microfilament Proteins / Q000235:genetics*; D011859:Radiography; D012720:Severity of Illness Index; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines