Deficient expression of the gene coding for decorin in a lethal form of Marfan syndrome.
The markedly decreased level of the messenger RNA of decorin, an abundant dermatan/chondroitin sulfate proteoglycan was found in the skin fibroblast culture of a lethally sick Marfan infant. Also, the amount of decorin polypeptide in the culture medium of the fibroblasts of this infant was markedly decreased. When the effect of interleukin-1 beta on the transcription of decorin was tested in these fibroblasts, the response was deficient as compared to control fibroblasts whereas transcription of type I and III collagen genes and versican was stimulated normally. The decreased decorin mRNA level, unresponsive to interleukin-1 beta in this lethally sick Marfan patient, stresses the significance of this proteoglycan in the formation of normal connective tissue. Furthermore, the low expression of this gene could be responsible for the connective tissue findings in this patient, representing a rare type of Marfan syndrome. The identical finding in three other, unrelated Marfan individuals suggests a more general significance of deficient decorin expression in this disease.
Department of Clinical Genetics, Kuopio University Central Hospital, Finland.
L
L
Pulkkinen
K
K
Kainulainen
T
T
Krusius
P
P
Mäkinen
J
J
Schollin
K H
KH
Gustavsson
L
L
Peltonen
D015153:Blotting, Western; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D005804:Genes, Lethal; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger