Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.
We have studied a patient with severe, dominantly inherited Ehlers-Danlos syndrome type IV. The results indicate that this patient carries a deletion of 3.3 kilo-base pairs in the triple helical coding domain of one of the two alleles for the pro-alpha-chains of type III collagen (COL3A1). His cultured skin fibroblasts contain equal amounts of normal length mRNA and of mRNA shortened by approximately 600 bases, and synthesize both normal and shortened pro-alpha 1(III)-chains. In procollagen molecules containing one or more shortened chains, a triple helix is formed with a length of only about 780 amino acids. The mutant procollagen molecules have decreased thermal stability, are less efficiently secreted, and are not processed as their normal counterpart. The deletion in this family is the first mutation to be described in COL3A1.
Superti-Furga
A
A
Department of Pediatrics, University of Zurich, Switzerland.
Gugler
E
E
Gitzelmann
R
R
Steinmann
B
B
D000328:Adult; D000483:Alleles; D001345:Autoradiography; D002872:Chromosome Deletion; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D010449:Peptide Mapping; D010641:Phenotype; D011347:Procollagen / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000648:ultrastructure
D011347:Procollagen; D012333:RNA, Messenger; D004262:DNA Restriction Enzymes