DSP Gene

DSP (DSP is the acronym for desmoplakin) is a protein-coding gene located on chromosome 6p24.3. The encoded protein, desmoplakin belongs to the intermediate filaments that are anchored to desmosomal plaques and thus forms an obligatory component of functional desmosomes . Desmoplakin is highly expressed in several tissues (keratinocytes, cardiac muscle), but hardly in the adult brain and not in skeletal muscle or leukocytes. An important paralogue of this gene is EPPK1.

Mutations in the DSP gene are the cause of several cardiomyopathies and keratinization abnormalities. These include:

• Arrhythmogenic right ventricular dysplasia 8 with mutations in desmoplakin (AD) OMIM: 607450
• Keratosis palmoplantaris with mutations in desmoplakin (Carjaval-Huerto 1998) Dilated cardiomyopathy, woolly hair, striated keratosis palmoplantaris with mutations in desmoplakin (AR), OMIM: 605676
• Dilated cardiomyopathy, woolly hair, keratosis palmoplantaris, dental agenesis with mutations in desmoplakin (AD) OMIM: 615821
• Acantholytic epidermolysis bullosa with mutations in desmoplakin (AR) OMIM: 609638 (SAM syndrome: lethal recessive form of epidermolysis bullosa combined with keratosis palmoplantaris, onychodysptrophy, alopecia universalis and severe cardiomyopathy)
• Keratosis palmoplantaris striata II with mutations in desmoplakin (AD) OMIM: 612908
• Skin fragility syndrome with woolly hair and mutations in desmoplakin (AR) OMIM: 607655

Desmoplakin is one of the major components of the desmosome. It belongs to a large family of proteins called the plakin family. These large molecules connect cytoskeletal networks to the plasma membrane and integrate actin, microtubules and intermediate filaments. It is a large protein (~ 210-250 kD depending on isoform) that specifically links desmocollins and desmogleins to the intermediate filament network (desmin) through interaction with plakoglobin and plakophilin. Several studies have demonstrated the importance of desmoplakin in desmosome structure and function. Mice lacking desmoplakin die around the time of implantation and have fewer desmosomes.

Desmoplakin is a specific marker for lymphatic vessels and can be visualized by light microscopy with an anti-desmoplakin antibody lymphatic vessels (Ebata Net al. 2001).

Desmoplakin antibodies can be detected in paraneoplastic pemphigus. In this autoimmune disease, in addition to desmoplakin I (250 kd) antibodies, the following antibodies are detected: bullous pemphigoid antigen I (230 kd), desmoplakin II (210 kd), envoplakin (210 kd), periplakin (190 kd), plectin (500 kd) and a 170-kd protein (alpha-2-macroglobulin-like-1) Yong AA et al (2013).

1. Ebata Net al. (2001) Desmoplakin as a specific marker of lymphatic vessels. Microvasc Res 61:40-48.
2. Erolu E et al (2018) Arrhythmogenic right ventricular dysplasia, cutaneous manifestations and desmoplakin mutation: Carvajal syndrome. Pediatr Int 60: 987-989.
3. Liang J et al. (2019) Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome caused by de novo mutation in the DSP gene misdiagnosed as generalized pustular psoriasis and treatment of acitretin with gabapentin. J Dermatol 46: 622-625.
4. Polivka L et al. (2016) Combination of palmoplantar keratoderma and hair shaft anomalies, the warning signal of severe arrhythmogenic cardiomyopathy: a systematic review on genetic desmosomal diseases. J Med Genet 53:289-295.
5. Tayeh C et al (2019) Mutation in the SR6 region of desmoplakin is associated with pustular psoriasiform rash and left ventricular dysfunction. Int J Dermatol 58:742-744
6. Yong AA et al (2013) Paraneoplastic pemphigus. Australas J Dermatol 54: 241-250.