|RNA expression pattern|
The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Alternative splicing results in two transcript variants encoding distinct isoforms.
Desmocollin-3 is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. The loss of these components leads to a lack of adhesion and a gain of cellular mobility.
A consanguineous Afghan family in which 3 sisters, 12 to 18 years of age, and their 5-year-old brother displayed features of hereditary hypotrichosis, associated with vesicles on the scalp and skin. At birth, scalp hair was present, and after ritual shaving at 1 week of age, scalp hair grew back; however, the hair was fragile and began falling out at 2 to 3 months of age, eventually leaving only sparse hair on the scalp. Vesicles that were less than 1 cm in diameter were observed on the scalp and skin of most of the body, occasionally disappearing but then reappearing; intermittently, the vesicles would burst with a release of fluid, leaving scars on the site that took 3 to 4 months to heal. There were no mucosal vesicles. Upon examination, the affected individuals were nearly devoid of eyebrows, eyelashes, axillary hair, and body hair. Teeth, nails, palms, soles, sweating, and hearing were normal, as was electrocardiography. Serum IgA, IgE, and IgD were measured in 1 individual and showed no change compared to controls. The parents were clinically unaffected. A scalp biopsy of the 18-year-old sister showed slight follicular plugging, mild perivascular and periadnexal inflammatory cell presence, and normal hair follicles. The sebaceous glands appeared morphologically normal and connected to the hair follicles.
Genotyping and linkage analysis of the consanguineous Afghan family resulted in a maximum 2-point load score of 2.68 (theta = 0.0) at markers D18S36 and D18S547. Multipoint analysis generated a maximum load score of 3.30 at marker D18S877. Recombination events defined an 8.30-cM critical interval on chromosome 18q12.1, flanked by markers D18S66 and D18S1139, containing 30 genes.
A a nonsense mutation in the DSC3 gene (600271.0001) mapping to chromosome 18q12.1 was identified in the onsanguineous Afghan family with hypotrichosis and recurrent skin vesicles (613102). The unaffected parents and 3 healthy sibs were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls. In affected members of this family with hypotrichosis were homozygous for a 2129T-G transversion in exon 14 of the DSC3 gene, resulting in a leu710-to-ter (L710X) (Ayub et al. 2009)substitution at the junction of the transmembrane and the C-terminal cytoplasmic domain, predicted to cause premature termination and nonsense mediated decay of the mRNA or instability of the truncated protein. The unaffected parents and 3 healthy sibs were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls.
- Amagai M, Wang Y, Minoshima S, Kawamura K, Green KJ, Nishikawa T, Shimizu N (Jul 1995). "Assignment of the human genes for desmocollin 3 (DSC3) and desmocollin 4 (DSC4) to chromosome 18q12". Genomics 25 (1): 330–2. doi:10.1016/0888-7543(95)80154-E. PMID 7774948.
- Buxton RS, Cowin P, Franke WW, Garrod DR, Green KJ, King IA, Koch PJ, Magee AI, Rees DA, Stanley JR, et al. (Jun 1993). "Nomenclature of the desmosomal cadherins". J Cell Biol 121 (3): 481–3. doi:10.1083/jcb.121.3.481. PMC 2119574. PMID 8486729.
- "Entrez Gene: DSC3 desmocollin 3".
- Oshiro MM, Kim CJ, Wozniak RJ, Junk DJ, Muñoz-Rodríguez JL, Burr JA, Fitzgerald M, Pawar SC, Cress AE, Domann FE, Futscher BW (2005). "Epigenetic silencing of DSC3 is a common event in human breast cancer". Breast Cancer Res. 7 (5): R669–80. doi:10.1186/bcr1273. PMC 1242132. PMID 16168112.
- Ayub M, Basit S, Jelani M, Ur Rehman F, Iqbal M, Yasinzai M, Ahmad W (October 2009). "A Homozygous Nonsense Mutation in the Human Desmocollin-3 (DSC3) Gene Underlies Hereditary Hypotrichosis and Recurrent Skin Vesicles". Am. J. Hum. Genet. 85 (4): 515–20. doi:10.1016/j.ajhg.2009.08.015. PMC 2756559. PMID 19765682.
- Bonné S, Gilbert B, Hatzfeld M, Chen X, Green KJ, van Roy F (April 2003). "Defining desmosomal plakophilin-3 interactions". J. Cell Biol. 161 (2): 403–16. doi:10.1083/jcb.200303036. PMC 2172904. PMID 12707304.
- Arnemann J, Spurr NK, Wheeler GN, et al. (1991). "Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP)". Genomics 10 (3): 640–5. doi:10.1016/0888-7543(91)90446-L. PMID 1889810.
- King IA, Sullivan KH, Bennett R, Buxton RS (1995). "The desmocollins of human foreskin epidermis: identification and chromosomal assignment of a third gene and expression patterns of the three isoforms". J. Invest. Dermatol. 105 (3): 314–21. doi:10.1111/1523-1747.ep12319935. PMID 7665906.
- Kawamura K, Watanabe K, Suzuki T, et al. (1994). "cDNA cloning and expression of a novel human desmocollin". J. Biol. Chem. 269 (42): 26295–302. PMID 7929347.
- Buxton RS, Wheeler GN, Pidsley SC, et al. (1994). "Mouse desmocollin (Dsc3) and desmoglein (Dsg1) genes are closely linked in the proximal region of chromosome 18". Genomics 21 (3): 510–6. doi:10.1006/geno.1994.1309. PMID 7959727.
- Nuber UA, Schäfer S, Stehr S, et al. (1997). "Patterns of desmocollin synthesis in human epithelia: immunolocalization of desmocollins 1 and 3 in special epithelia and in cultured cells". Eur. J. Cell Biol. 71 (1): 1–13. PMID 8884173.
- Kurzen H, Moll I, Moll R, et al. (1998). "Compositionally different desmosomes in the various compartments of the human hair follicle". Differentiation 63 (5): 295–304. doi:10.1046/j.1432-0436.1998.6350295.x. PMID 9810708.
- Moll I, Houdek P, Schäfer S, et al. (1999). "Diversity of desmosomal proteins in regenerating epidermis: immunohistochemical study using a human skin organ culture model". Arch. Dermatol. Res. 291 (7–8): 437–46. doi:10.1007/s004030050435. PMID 10482015.
- Hanakawa Y, Amagai M, Shirakata Y, et al. (2000). "Different effects of dominant negative mutants of desmocollin and desmoglein on the cell-cell adhesion of keratinocytes". J. Cell. Sci. 113 (10): 1803–11. PMID 10769211.
- Whittock NV, Hunt DM, Rickman L, et al. (2000). "Genomic organization and amplification of the human desmosomal cadherin genes DSC1 and DSC3, encoding desmocollin types 1 and 3". Biochem. Biophys. Res. Commun. 276 (2): 454–60. doi:10.1006/bbrc.2000.3500. PMID 11027496.
- Gadhavi PL, Greenwood MD, Strom M, et al. (2001). "The regulatory region of the human desmocollin 3 promoter forms a DNA four-way junction". Biochem. Biophys. Res. Commun. 281 (2): 520–8. doi:10.1006/bbrc.2001.4375. PMID 11181078.
- Klus GT, Rokaeus N, Bittner ML, et al. (2001). "Down-regulation of the desmosomal cadherin desmocollin 3 in human breast cancer". Int. J. Oncol. 19 (1): 169–74. PMID 11408939.
- Weiske J, Schöneberg T, Schröder W, et al. (2001). "The fate of desmosomal proteins in apoptotic cells". J. Biol. Chem. 276 (44): 41175–81. doi:10.1074/jbc.M105769200. PMID 11500511.
- Hatzfeld M, Green KJ, Sauter H (2003). "Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains". J. Cell. Sci. 116 (Pt 7): 1219–33. doi:10.1242/jcs.00275. PMID 12615965.
- Bonné S, Gilbert B, Hatzfeld M, et al. (2003). "Defining desmosomal plakophilin-3 interactions". J. Cell Biol. 161 (2): 403–16. doi:10.1083/jcb.200303036. PMC 2172904. PMID 12707304.
- Oshiro MM, Watts GS, Wozniak RJ, et al. (2003). "Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression". Oncogene 22 (23): 3624–34. doi:10.1038/sj.onc.1206545. PMID 12789271.
- Zhang Y, Wolf-Yadlin A, Ross PL, et al. (2005). "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules". Mol. Cell Proteomics 4 (9): 1240–50. doi:10.1074/mcp.M500089-MCP200. PMID 15951569.