Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly.
Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to Marfan syndrome (MFS) and characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple congenital contractures and abnormalities of the external ears. In contrast to MFS, CCA does not affect the aorta or the eyes. Two closely related genes, FBN1 located on chromosome 15q15-21.3 and FBN2 located at 5q23-31, encode large fibrillin proteins found in extracellular matrix structures called microfibrils. The MFS is caused by mutations in FBN1, while CCA has been genetically linked to FBN2 (refs 2, 5, 6). We now describe a pair of FBN2 missense mutations in two CCA patients that cause substitution of distinct cysteine residues in separate epidermal growth-factor-like (EGF) repeats. Our study provides final proof of the association between FBN2 mutations and CCA pathology, thus establishing the role of the fibrillin-2 in extracellular matrix physiology and pathology.
D001483:Base Sequence; D002460:Cell Line; D003545:Cysteine; D004252:DNA Mutational Analysis; D004815:Epidermal Growth Factor / Q000235:genetics; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005347:Fibroblasts; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D054392:Adipokines
D003545:Cysteine; D004815:Epidermal Growth Factor; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human