Alternative titles; symbols
HGNC Approved Gene Symbol: DCN
SNOMEDCT: 702359002;
Cytogenetic location: 12q21.33 Genomic coordinates (GRCh38): 12:91,140,484-91,182,817 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q21.33 | Corneal dystrophy, congenital stromal | 610048 | Autosomal dominant | 3 |
Decorin (DCN) is a small proteoglycan that interacts with type I collagen fibrils, thereby influencing the kinetics of fibril formation and the distance between adjacent collagen fibrils (Schonherr et al., 1995).
Danielson et al. (1993) reported that the deduced DCN protein contains an N-terminal propeptide sequence, followed by a single glycosaminoglycan attachment site, a cysteine-rich region, and 10 tandem, leucine-rich repeats of a nominal 24-residue consensus sequence. Using Northern blot analysis or RT-PCR, they detected 2 alternatively spliced leader exons of the DCN gene in a variety of mRNAs isolated from human cell lines and tissues. Sequences highly homologous (74-87%) to exons Ia and Ib were found in the 5-prime untranslated region of avian and bovine decorin, respectively. This high degree of conservation among species suggested regulatory functions for these leader exons.
In situ hybridization studies of developing mouse embryos suggested that decorin may play a role in epithelial/mesenchymal interactions during organ development and shaping (Scholzen et al., 1994).
Danielson et al. (1993) found that the human decorin gene spans more than 38 kb and contains 8 exons and very large introns, 2 of which are 5.4 and more than 13.2 kb. They discovered 2 alternatively spliced leader exons, Ia and Ib, in the 5-prime untranslated region.
By Southern analysis of a panel of human-rodent somatic cell hybrid DNAs with cDNA probes, McBride et al. (1990) assigned the DCN gene to chromosome 12. Regionalization to 12p12.1-qter was obtained by examining hybrids containing spontaneous breaks or well-characterized translocations involving chromosome 12. Hybridization with subfragment cDNA probes suggested the presence of 2 copies of the DCN gene, or related sequences, at the locus on chromosome 12, although there was no evidence for the function of more than one DCN gene. By in situ hybridization, Pulkkinen et al. (1992) placed the DCN gene at 12q21-q22. Vetter et al. (1993) mapped the human decorin gene by in situ hybridization to 12q21.3. Using a genomic clone as the labeled probe and in situ hybridization, Danielson et al. (1993) mapped the DCN gene to 12q23. They specifically noted that there were 4 times as many grains centered on 12q23 as on 12q21, where Pulkkinen et al. (1992) had placed the probable site. In a study of candidate genes for Noonan syndrome (163950), Ion et al. (2000) reassigned the map position of DCN to 12q13.2 using FISH. Scholzen et al. (1994) assigned the homologous gene in the mouse to chromosome 10, using interspecific backcrossing.
Vogel and Clark (1989) found little evidence that the metabolism of either decorin or biglycan (BGN; 301870) is altered by abnormalities in the structure or secretion of types I and III collagen. In a presumably homozygous case of the Marfan syndrome (154700) reported by Schollin et al. (1988), Pulkkinen et al. (1990) found markedly decreased level of mRNA for decorin, markedly decreased decorin polypeptide in the culture medium of fibroblasts from the infant, and deficient effect of interleukin-1-beta (147720) on the transcription of decorin as tested in these fibroblasts. In 3 of 12 other unrelated Marfan patients, they also found deficient decorin expression.
By immunogold labeling, Schonherr et al. (1995) found that both decorin and biglycan distributed along collagen fibrils in human MG-63 osteosarcoma cell collagen lattices and in human skin. Recombinant biglycan and decorin showed lower dissociation constants than their glycanated forms. Decorin competed with biglycan for collagen binding, suggesting that both proteoglycans use identical or adjacent binding sites on the fibril.
Dyne et al. (1996) studied 2 patients with osteogenesis imperfecta and the same gly415-to-ser mutation of the COL1A1 gene (120150.0044), but a different clinical expression. They speculated that these differences could be the result of abnormalities in other connective tissue proteins. Since decorin is a component of connective tissue, binds to type I collagen fibrils, and plays a role in matrix assembly, they studied decorin production in skin fibroblasts from these 2 patients. Cultured fibroblasts from the patient with extremely severe osteogenesis imperfecta (classified as type II/III) were found to secrete barely detectable amounts of decorin into culture medium. Northern blot analysis showed decorin mRNA levels below the limit of detection. The patient with a less severe phenotype had fibroblasts that expressed decorin normally. Dyne et al. (1996) suggested that the different clinical phenotypes could be due to the differing genetic backgrounds of the patients, such that in the more severely affected patient the absence of decorin aggravated the clinical phenotype.
When expressed ectopically, decorin is capable of suppressing the growth of various tumor cell lines. Moscatello et al. (1998) demonstrated that it induced a marked growth suppression in A431 squamous carcinoma cells, when either exogenously added or endogenously produced by a transgene. Decorin caused rapid phosphorylation of the EGF receptor (131550) and a concurrent activation of mitogen-activated protein (MAP) kinase signal pathway. Thus, EGF and decorin converge functionally to regulate the cell cycle through activation of a common pathway that ultimately leads to growth suppression.
Wiberg et al. (2001) found that both biglycan and decorin showed a strong affinity for type VI collagen (see COL6A1, 120220) extracted from human placenta. Digestion of the glycosaminoglycan side chains did not significantly affect binding. Both proteoglycans bound type VI collagen and competed equally with each other, suggesting that they bound to the same site on type VI collagen. Electron microscopy confirmed that biglycan and decorin bound exclusively to a domain close to the interface between the N terminus of the collagen triple-helical region and the following globular domain. Type VI collagen alpha-2 (COL6A2; 120240) appeared to play a role in the interaction.
Using purified bovine proteins and fetal bovine nuchal ligament tissue, Reinboth et al. (2002) found that both biglycan and decorin bound the elastic fiber component tropoelastin (see ELN, 130160) and fibrillin (FBN1; 134797)-containing microfibrils. They did not bind the elastin-binding proteins Magp1 (MFAP2; 156790) and Magp2 (MFAP5; 601103). The isolated core biglycan and decorin proteins bound to tropoelastin more strongly than the intact proteoglycans, and biglycan bound tropoelastin more avidly than decorin. Blocking experiments suggested that biglycan and decorin bound closely spaced yet distinct sites on tropoelastin. Addition of Magp1 enhanced the binding of biglycan, but not decorin, to tropoelastin. Magp1 interacted with biglycan, but not decorin, in solution.
In a family with congenital stromal corneal dystrophy (CSCD; 610048), Bredrup et al. (2005) identified a heterozygous 1-bp deletion in the last exon, which they erroneously labeled exon 10 (Rodahl, 2009), of the DCN gene (125255.0001). The deletion was found in all affected family members but not in any healthy family member or in 200 normal controls.
In a Belgian mother and son with CSCD, Rodahl et al. (2006) identified heterozygosity for a 1-bp deletion in the DCN gene (125255.0002), causing a frameshift predicted to result in a stop codon at the same codon as the frameshift mutation (125255.0001) in the Norwegian family studied by Bredrup et al. (2005).
In a Korean mother and daughter with CSCD, Kim et al. (2011) identified heterozygosity for a 1-bp deletion in DCN (125255.0003).
In 5 affected members of a 3-generation Chinese family segregating autosomal dominant CSCD, Jing et al. (2014) identified heterozygosity for a 1-bp deletion in the DCN gene (125255.0004) that was not present in unaffected family members or in 50 healthy controls. Jing et al. (2014) noted that all 4 CSCD-associated frameshift mutations that had been reported cause a premature termination codon with loss of the 33 C-terminal amino acids of the decorin proteoglycan, suggesting that exon 8 is a mutational hotspot and a functionally important region of DCN.
In a Norwegian family originally reported by Odland (1968) with congenital stromal corneal dystrophy (CSCD; 610048), Bredrup et al. (2005) identified a heterozygous 1-bp deletion (967delT) in the last exon, which they erroneously labeled exon 10 (Rodahl, 2009), of the DCN gene. The mutation was predicted to lead to a frameshift, alteration of 4 amino acids, and loss of the C-terminal 33 amino acids (Ser323fsTer5). Bredrup et al. (2005) postulated that the defective interaction of mutant decorin with collagen would disturb the regularity of corneal collagen in affected heterozygotes.
In a Belgian mother and son with congenital stromal corneal dystrophy (CSCD; 610048), originally reported by Van Ginderdeuren et al. (2002), Rodahl et al. (2006) identified heterozygosity for a 1-bp deletion (c.941delC) in exon 10 of the DCN gene, causing a frameshift resulting in a premature termination codon (Pro314fsTer14) at the same codon as the frameshift mutation (125255.0001) in the Norwegian family studied by Bredrup et al. (2005). Both mutations are predicted to result in loss of the C-terminal 33 amino acids. Kim et al. (2011) suggested that 'exon 10' in the report by Rodahl et al. (2006) was a misprint for 'exon 8,' since the DCN gene has only 8 exons.
In a Korean mother and daughter with congenital stromal corneal dystrophy (CSCD; 610048), Kim et al. (2011) identified heterozygosity for a 1-bp deletion (c.947delG) in exon 8 of the DCN gene, causing a frameshift predicted to result in a premature termination codon (Gly316AspfsTer12). The mutation was not found in the proband's unaffected son. Kim et al. (2011) noted that this mutation results in a termination codon after residue 327, the same site as in the 2 previously reported frameshift mutations in CSCD families (125255.0001 and 125255.0002).
In 5 affected members of a 3-generation Chinese family segregating autosomal dominant CSCD (610048), Jing et al. (2014) identified heterozygosity for a 1-bp deletion (c.962delA) in exon 8 of the DCN gene that was not present in unaffected family members or in 50 healthy controls, causing a frameshift predicted to result in a premature termination codon (Lys321ArgfsTer7) and loss of the 33 C-terminal amino acids of the decorin proteoglycan.
Bredrup, C., Knappskog, P. M., Majewski, J., Rodahl, E., Boman, H. Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene. Invest. Ophthal. Vis. Sci. 46: 420-426, 2005. [PubMed: 15671264] [Full Text: https://doi.org/10.1167/iovs.04-0804]
Danielson, K. G., Fazzio, A., Cohen, I., Cannizzaro, L. A., Eichstetter, I., Iozzo, R. V. The human decorin gene: intron-exon organization, discovery of two alternatively spliced exons in the 5-prime untranslated region, and mapping of the gene to chromosome 12q23. Genomics 15: 146-160, 1993. [PubMed: 8432526] [Full Text: https://doi.org/10.1006/geno.1993.1022]
Dyne, K. M., Valli, M., Forlino, A., Mottes, M., Kresse, H., Cetta, G. Deficient expression of the small proteoglycan decorin in a case of severe/lethal osteogenesis imperfecta. Am. J. Med. Genet. 63: 161-166, 1996. [PubMed: 8723103] [Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<161::AID-AJMG28>3.0.CO;2-L]
Ion, A., Crosby, A. H., Kremer, H., Kenmochi, N., Van Reen, M., Fenske, C., Van Der Burgt, I., Brunner, H. G., Montgomery, K. Detailed mapping, mutation analysis, and intragenic polymorphism identification in candidate Noonan syndrome genes MYL2, DCN, EPS8, and RPL6. J. Med. Genet. 37: 884-886, 2000. [PubMed: 11185075] [Full Text: https://doi.org/10.1136/jmg.37.11.884]
Jing, Y., Kumar, P. R., Zhu, L., Edward, D. P., Tao, S., Wang, L., Chuck, R., Zhang, C. Novel decorin mutation in a Chinese family with congenital stromal corneal dystrophy. Cornea 33: 288-293, 2014. [PubMed: 24413633] [Full Text: https://doi.org/10.1097/ICO.0000000000000055]
Kim, J., Ko, J. M., Lee, I., Kim, J. Y., Kim, M. J., Tchah, H. A novel mutation of the decorin gene identified in a Korean family with congenital hereditary stromal dystrophy. Cornea 30: 1473-1477, 2011. [PubMed: 21993463] [Full Text: https://doi.org/10.1097/ICO.0b013e3182137788]
McBride, O. W., Fisher, L. W., Young, M. F. Localization of PGI (biglycan, BGN) and PGII (decorin, DCN, PG-40) genes on human chromosomes Xq13-qter and 12q, respectively. Genomics 6: 219-255, 1990. [PubMed: 1968422] [Full Text: https://doi.org/10.1016/0888-7543(90)90560-h]
Moscatello, D. K., Santra, M., Mann, D. M., McQuillan, D. J., Wong, A. J., Iozzo, R. V. Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J. Clin. Invest. 101: 406-412, 1998. [PubMed: 9435313] [Full Text: https://doi.org/10.1172/JCI846]
Odland, M. Dystrophia corneae parenchymatosa congenita: a clinical, morphological and histochemical examination. Acta Ophthal. 46: 477-485, 1968. [PubMed: 5304426] [Full Text: https://doi.org/10.1111/j.1755-3768.1968.tb02832.x]
Pulkkinen, L., Alitalo, T., Krusius, T., Peltonen, L. Expression of decorin in human tissues and cell lines and defined chromosomal assignment of the gene locus (DCN). Cytogenet. Cell Genet. 60: 107-111, 1992. [PubMed: 1611907] [Full Text: https://doi.org/10.1159/000133314]
Pulkkinen, L., Kainulainen, K., Krusius, T., Makinen, P., Schollin, J., Gustavsson, K.-H., Peltonen, L. Deficient expression of the gene coding for decorin in a lethal form of Marfan syndrome. J. Biol. Chem. 265: 17780-17785, 1990. [PubMed: 2211661]
Reinboth, B., Hanssen, E., Cleary, E. G., Gibson, M. A. Molecular interactions of biglycan and decorin with elastic fiber components. J. Biol. Chem. 277: 3950-3957, 2002. [PubMed: 11723132] [Full Text: https://doi.org/10.1074/jbc.M109540200]
Rodahl, E., Van Ginderdeuren, R., Knappskog, P. M., Bredrup, C., Boman, H. A second decorin frame shift mutation in a family with congenital stromal corneal dystrophy. Am. J. Ophthal. 142: 520-521, 2006. [PubMed: 16935612] [Full Text: https://doi.org/10.1016/j.ajo.2006.03.064]
Rodahl, E. Personal Communication. Baltimore, Md. 3/11/2009.
Schollin, J., Bjarke, B., Gustavson, K.-H. Probable homozygotic form of the Marfan syndrome in a newborn child. Acta Paediat. Scand. 77: 452-456, 1988. [PubMed: 3389143] [Full Text: https://doi.org/10.1111/j.1651-2227.1988.tb10679.x]
Scholzen, T., Solursh, M., Suzuki, S., Reiter, R., Morgan, J. L., Buchberg, A. M., Siracusa, L. D., Iozzo, R. V. The murine decorin: complete cDNA cloning, genomic organization, chromosomal assignment, and expression during organogenesis and tissue differentiation. J. Biol. Chem. 269: 28270-28281, 1994. [PubMed: 7961765]
Schonherr, E., Witsch-Prehm, P., Harrach, B., Robenek, H., Rauterberg, J., Kresse, H. Interaction of biglycan with type I collagen. J. Biol. Chem. 270: 2776-2783, 1995. [PubMed: 7852349] [Full Text: https://doi.org/10.1074/jbc.270.6.2776]
Van Ginderdeuren, R., De Vos, R., Casteels, I., Foets, B. Report of a new family with dominant congenital heredity stromal dystrophy of the cornea. Cornea 21: 118-120, 2002. [PubMed: 11805522] [Full Text: https://doi.org/10.1097/00003226-200201000-00025]
Vetter, U., Vogel, W., Just, W., Young, M. F., Fisher, L. W. Human decorin gene: intron-exon junctions and chromosomal localization. Genomics 15: 161-168, 1993. [PubMed: 8432527] [Full Text: https://doi.org/10.1006/geno.1993.1023]
Vogel, K. G., Clark, P. E. Small proteoglycan synthesis by skin fibroblasts cultured from elderly donors and patients with defined defects in types I and III collagen metabolism. Europ. J. Cell Biol. 49: 236-243, 1989. [PubMed: 2776773]
Wiberg, C., Hedbom, E., Khairullina, A., Lamande, S. R., Oldberg, A., Timpl, R., Morgelin, M., Heinegard, D. Biglycan and decorin bind close to the N-terminal region of the collagen VI triple helix. J. Biol. Chem. 276: 18947-18952, 2001. [PubMed: 11259413] [Full Text: https://doi.org/10.1074/jbc.M100625200]