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The substitution of glycine 661 by arginine in type III collagen produces mutant molecules with different thermal stabilities and causes Ehlers-Danlos syndrome type IV.
  1. A Richards,
  2. P Narcisi,
  3. J Lloyd,
  4. C Ferguson,
  5. F M Pope
  1. Dermatology Research Group, Clinical Research Centre, Harrow, Middlesex, UK.

    Abstract

    Previous studies have shown that Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutations of type III collagen (COL3A1). Here we have characterised the most amino-terminal glycine substitution so far described in a patient with EDS IV. A combination of peptide mapping and chemical cleavage analysis of cDNA localised the mutation in cyanogen bromide peptide CB5. Sequence analysis showed a G to A mutation, converting glycine 661 to arginine, which was a new dominant mutation. Analysis of type III collagen secreted by cultured fibroblasts showed an overmodified mutant protein with normal thermal stability. However, the intracellularly retained form melted 2 degrees C lower than normal. This indicated that molecules resulting from the same mutation can differ in their thermal stabilities.

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