Encyclopedia
Desmocollin 2: The DSC2 gene provides instructions for making a protein called desmocollin-2.
- genes
1. Normal Function
This protein is found in many tissues, although it appears to be particularly important in the heart muscle and skin. Desmocollin-2 is a major component of specialized structures called desmosomes. These structures help hold neighboring cells together, which provides strength and stability to tissues. Desmosomes may also be involved in other critical cell functions, including chemical signaling pathways, the process by which cells mature to perform specific functions (differentiation), and the self-destruction of cells (apoptosis).
2. Health Conditions Related to Genetic Changes
2.1 Keratoderma with Woolly Hair
At least one mutation in the DSC2 gene has been found to cause a form of keratoderma with woolly hair classified as type III. It is characterized by thick, calloused skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); coarse, dry, fine, and tightly curled hair; and a potentially life-threatening form of heart disease called arrhythmogenic right ventricular cardiomyopathy (ARVC).
The known mutation, which is written as 1841delG, deletes one DNA building block (base pair) from the DSC2 gene. The resulting abnormal version of the desmocollin-2 protein alters the structure of desmosomes, preventing cells from attaching to one another effectively. Researchers suspect that the impaired connections between cells make the skin, hair, and heart muscle more fragile. Over time, as these tissues are exposed to mechanical stress (for example, friction on the surface of the skin or the constant contraction and relaxation of the heart muscle), they become damaged and can no longer function normally. This mechanism probably underlies the skin, hair, and heart problems that occur in keratoderma with woolly hair type III. Studies suggest that abnormal cell signaling may also contribute to cardiomyopathy in people with this condition.
Several other mutations in the DSC2 gene cause ARVC without palmoplantar keratoderma or woolly hair. It is unclear why some mutations in this gene affect the skin and hair, while others do not.
2.2 Arrhythmogenic right ventricular cardiomyopathy
3. Other Names for This Gene
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ARVD11
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cadherin family member 2
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CDHF2
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desmocollin-2 isoform Dsc2a preproprotein
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desmocollin-2 isoform Dsc2b preproprotein
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desmosomal glycoprotein II/III
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DG2
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DGII/III
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DSC3
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/dsc2
References
- De Bortoli M, Beffagna G, Bauce B, Lorenzon A, Smaniotto G, Rigato I, CaloreM, Li Mura IE, Basso C, Thiene G, Lanfranchi G, Danieli GA, Nava A, Rampazzo A.The p.A897KfsX4 frameshift variation in desmocollin-2 is not a causative mutationin arrhythmogenic right ventricular cardiomyopathy. Eur J Hum Genet. 2010Jul;18(7):776-82. doi: 10.1038/ejhg.2010.19.
- Gehmlich K, Syrris P, Peskett E, Evans A, Ehler E, Asimaki A, Anastasakis A,Tsatsopoulou A, Vouliotis AI, Stefanadis C, Saffitz JE, Protonotarios N, McKenna WJ. Mechanistic insights into arrhythmogenic right ventricular cardiomyopathycaused by desmocollin-2 mutations. Cardiovasc Res. 2011 Apr 1;90(1):77-87. doi:10.1093/cvr/cvq353.
- Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B. Mutantdesmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J HumGenet. 2006 Dec;79(6):1081-8.
- Lorenzon A, Pilichou K, Rigato I, Vazza G, De Bortoli M, Calore M, Occhi G,Carturan E, Lazzarini E, Cason M, Mazzotti E, Poloni G, Mostacciuolo ML, DalientoL, Thiene G, Corrado D, Basso C, Bauce B, Rampazzo A. Homozygous Desmocollin-2Mutations and Arrhythmogenic Cardiomyopathy. Am J Cardiol. 2015 Oct15;116(8):1245-51. doi: 10.1016/j.amjcard.2015.07.037.
- Simpson MA, Mansour S, Ahnood D, Kalidas K, Patton MA, McKenna WJ, Behr ER,Crosby AH. Homozygous mutation of desmocollin-2 in arrhythmogenic rightventricular cardiomyopathy with mild palmoplantar keratoderma and woolly hair.Cardiology. 2009;113(1):28-34. doi: 10.1159/000165696.
- Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKennaWJ. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated withmutations in the desmosomal gene desmocollin-2. Am J Hum Genet. 2006Nov;79(5):978-84.
