ARVC in Carvajal syndrome is associated with woolly hair and palmoplantar keratodermia, as a consequence of homozygous DSP mutations in the
desmoplakin gene located in the 6p24.3 locus (Table 1) [11, 24].
Desmoplakin: Mutations in the
desmoplakin gene have been identified in the causation of ARVD/C-8 and arrhythmogenic left ventricular cardiomyopathy (ALVC) (48,49).
Intestine Ensembl Gene ID Gene Symbol Gene Description ENSSSCG00000002523 CDC42BP B CDC42 binding protein kinase beta (DMPK-like) [Source :HGNC Symbol;Acc:1738] ENSSSCG00000019556 7SK.46 7SK RNA [Source:RFAM;Acc:RF00100] ENSSSCG00000012939 BRMS1 breast cancer metastasis suppressor 1 [Source:HGNC Symbol;Acc:17262] ENSSSCG00000013658 S1PR2 sphingosine-1-phosphate receptor 2 [Source:HGNC Symbol;Acc:3169] ENSSSCG00000026161 E2F6 E2F transcription factor 6 [Source:HGNC Symbol;Acc:3120] ENSSSCG00000001025 DSP
desmoplakin [Source:HGNC Symbol;Acc:3052] ENSSSCG00000014802 NUMA1 nuclear mitotic apparatus protein 1 [Source:HGNC Symbol;Acc:8059] ENSSSCG00000016912 PPAP2A phosphatidic acid phosphatase type 2A [Source:HGNC Symbol;Acc:9228] ENSSSCG00000030936 CH242-154K8.2 b.
[11] Carvajal disease is similar clinically to Naxos disease, except for left ventricular involvement and presentation at a younger age, and it is due to mutation in the
desmoplakin gene.
Mutations in the plakoglobin (PKG; MIM 173325) and
desmoplakin (DSP; MIM 125647) genes have been reported to cause the Naxos disease and the Carvajal syndrome, respectively.2,3 Furthermore, a homozygous deletion mutation (c.1841delG) in desmocollin-2 (DSC2; MIM 125645) gene has been reported to be associated with cardiomyopathy and mild palmoplantar keratoderma in association with WH phenotype.4
By additional proteolysis and sequencing, we have found many cross-links within involucrin and between such proteins as involucrin and
desmoplakin, or cystatin [Alpha], or envoplakin, or loricrin and SPRs.
The identified possible contaminants were: filaggrin 2, glyceraldehyde-3-phosphate dehydrogenase, deleted in malignant brain tumors 1 protein, isoform DPI of
desmoplakin, prolactin-inducible protein, and serpin B12.
Although the mechanism by which the desmosomal cadherin-plakoglobin complex is coupled specifically to the IF cytoskeleton is unknown,
desmoplakin (DP) is a putative link.
Desmoplakin (DSP) and plakophilins (PKPs) are proteins associated with desmosome formation although they also have been shown to have other functions, for example transcriptional regulation.