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.
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.
Richards
A
A
Dermatology Research Group, Clinical Research Centre, Harrow, Middlesex, UK.
Narcisi
P
P
Lloyd
J
J
Ferguson
C
C
Pope
F M
FM
D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D005260:Female; D005998:Glycine / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*
D003094:Collagen; D001120:Arginine; D005998:Glycine