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

被引:14
作者
RICHARDS, A
NARCISI, P
LLOYD, J
FERGUSON, C
POPE, FM
机构
[1] Dermatology Research Group, Clinical Research Centre, Harrow, Middlesex HA1 3UJ, Watford Road
关键词
D O I
10.1136/jmg.30.8.690
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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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页码:690 / 693
页数:4
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