The DSP gene provides instructions for making a protein called desmoplakin. This protein is found primarily in cells of the heart and skin, where it 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).
Health Conditions Related to Genetic Changes
Keratoderma with woolly hair
Several mutations in the DSP gene have been found to cause a form of keratoderma with woolly hair classified as type II. This form of the condition is also known as Carvajal syndrome. 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 dilated left ventricular cardiomyopathy.
The DSP gene mutations that cause keratoderma with woolly hair type II lead to the production of an abnormally short version of the desmoplakin protein. The abnormal 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 II. Studies suggest that abnormal cell signaling may also contribute to cardiomyopathy in people with this condition.More About This Health Condition
Arrhythmogenic right ventricular cardiomyopathy
MedlinePlus Genetics provides information about Arrhythmogenic right ventricular cardiomyopathyMore About This Health Condition
Idiopathic pulmonary fibrosis
MedlinePlus Genetics provides information about Idiopathic pulmonary fibrosisMore About This Health Condition
DSP gene mutations have also been found to cause a spectrum of signs and symptoms that overlap with those of keratoderma with woolly hair type II (described above). A few families have had similar skin, hair, and heart abnormalities plus missing or unusually small teeth. Other families have had skin and hair abnormalities similar to keratoderma with woolly hair type II but no apparent heart problems. Still others have had palmoplantar keratoderma only, without any other features. DSP gene mutations can also cause a potentially life-threatening form of heart disease called arrhythmogenic right ventricular cardiomyopathy (ARVC) without abnormalities of the skin and hair. Although these conditions are all related to impaired function of desmoplakin and abnormal desmosomes, it is unclear how mutations in this gene lead to these different patterns of features.
At least four mutations in the DSP gene have been identified in people with a disorder called lethal acantholytic epidermolysis bullosa (LAEB). Features of this condition include very fragile skin that blisters and detaches easily, a complete absence of hair (alopecia), abnormal or missing fingernails, teeth that are present from birth (neonatal teeth), and abnormalities of the heart muscle (cardiomyopathy). The skin abnormalities lead to a severe loss of fluids and death in early infancy. Like the mutations that cause keratoderma with woolly hair type II, the mutations associated with LAEB lead to an abnormally short version of desmoplakin and impaired function of desmosomes. However, the protein associated with LAEB is missing additional regions, which probably accounts for the more severe signs and symptoms associated with this condition.
Other Names for This Gene
- 250/210 kDa paraneoplastic pemphigus antigen
- desmoplakin I
- desmoplakin II
- desmoplakin isoform I
- desmoplakin isoform II
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
- Bolling MC, Veenstra MJ, Jonkman MF, Diercks GF, Curry CJ, Fisher J, Pas HH, Bruckner AL. Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart. Br J Dermatol. 2010 Jun;162(6):1388-94. doi: 10.1111/j.1365-2133.2010.09668.x. Epub 2010 Mar 10. Citation on PubMed
- Chalabreysse L, Senni F, Bruyere P, Aime B, Ollagnier C, Bozio A, Bouvagnet P. A new hypo/oligodontia syndrome: Carvajal/Naxos syndrome secondary to desmoplakin-dominant mutations. J Dent Res. 2011 Jan;90(1):58-64. doi: 10.1177/0022034510383984. Epub 2010 Oct 12. Citation on PubMed
- Hobbs RP, Han SY, van der Zwaag PA, Bolling MC, Jongbloed JD, Jonkman MF, Getsios S, Paller AS, Green KJ. Insights from a desmoplakin mutation identified in lethal acantholytic epidermolysis bullosa. J Invest Dermatol. 2010 Nov;130(11):2680-3. doi: 10.1038/jid.2010.189. Epub 2010 Jul 8. No abstract available. Citation on PubMed or Free article on PubMed Central
- Jonkman MF, Pasmooij AM, Pasmans SG, van den Berg MP, Ter Horst HJ, Timmer A, Pas HH. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa. Am J Hum Genet. 2005 Oct;77(4):653-60. doi: 10.1086/496901. Epub 2005 Aug 17. Citation on PubMed or Free article on PubMed Central
- Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, Whittock N, Leigh IM, Stevens HP, Kelsell DP. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000 Nov 1;9(18):2761-6. doi: 10.1093/hmg/9.18.2761. Citation on PubMed
- Pigors M, Schwieger-Briel A, Cosgarea R, Diaconeasa A, Bruckner-Tuderman L, Fleck T, Has C. Desmoplakin mutations with palmoplantar keratoderma, woolly hair and cardiomyopathy. Acta Derm Venereol. 2015 Mar;95(3):337-40. doi: 10.2340/00015555-1974. Citation on PubMed
- Rasmussen TB, Hansen J, Nissen PH, Palmfeldt J, Dalager S, Jensen UB, Kim WY, Heickendorff L, Molgaard H, Jensen HK, Sorensen KE, Baandrup UT, Bross P, Mogensen J. Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms. Clin Genet. 2013 Jul;84(1):20-30. doi: 10.1111/cge.12056. Epub 2012 Dec 3. Citation on PubMed
- Yang Z, Bowles NE, Scherer SE, Taylor MD, Kearney DL, Ge S, Nadvoretskiy VV, DeFreitas G, Carabello B, Brandon LI, Godsel LM, Green KJ, Saffitz JE, Li H, Danieli GA, Calkins H, Marcus F, Towbin JA. Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Res. 2006 Sep 15;99(6):646-55. doi: 10.1161/01.RES.0000241482.19382.c6. Epub 2006 Aug 17. Citation on PubMed
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