title: Phenotype presentation for a novel mutation affecting a conserved cysteine residue in exon 63 of fibrillin-1 (Cys2633Arg).
abstract: Marfan syndrome is an autosomal dominant disease caused by mutations in the gene encoding for fibrillin-1 (FBN1). More than 1,000 FBN1 mutations have been identified, which may lead to multiple organ involvement, particularly of the ocular, skeletal, and cardiovascular systems. Mutations in exons 59-65 have been reported in the past to cause mild Marfan-like fibrillinopathies. We report a family with a mutation in exon 63 that manifests with significant cardiovascular system involvement such as aortic root dilatations, dissection of the aorta, and sudden death at a young age. Genetic analysis revealed that four related individuals are positive for a novel heterozygous Cys2633Arg mutation in exon 63. Their genotype-phenotype profile (based on the revised Ghent nosology) is described. We postulate that the Cys2633Arg mutation may manifest with significant and progressive enlargement of the aortic root, risk of aortic dissections, and minor skeletal abnormalities, without involving the ocular system (i.e., ectopia lentis).
authors: Department of Pediatrics, McMaster University, Hamilton, ON, Canada, stevici@hotmail.ca.
authors: Ivan
authors: I
authors: Stevic
authors: Mariya
authors: M
authors: Kozenko
authors: Robert
authors: R
authors: Lostracco
authors: Anthony K C
authors: AK
authors: Chan
authors: Howard H W
authors: HH
authors: Chan
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003545:Cysteine / Q000235:genetics*; D005091:Exons; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D054392:Adipokines
chemical_list: D003545:Cysteine; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines