A de novo variant in the ASPRV1 gene in a dog with ichthyosis

abstract: ...Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding aspartic peptidase, retroviral-like 1, which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.

... Analysis Techniques Gene Expression and Vector Techniques Protein Expression Research and Analysis Methods Molecular Biology Techniques Molecular Biology Assays and Analysis Techniques Gene Expression and Vector Techniques Protein Expression Research and Analysis Methods Specimen Preparation and Treatment Staining Immunofluorescence Staining A de novo variant in the ASPRV1 gene in a dog with ichthyosis ASPRV1 variant in a dog with tchthyosis Bauer Anina 1 2 http://orcid.org/0000-0003-1352-6282 Waluk

... genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding aspartic peptidase, retroviral-like 1, which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses. Author summary The skin undergoes a constant process of self-renewing and keratinocytes migrate

... several enzymes including proteases. In the present study, we sequenced the genome of a dog with a novel form of ichthyosis. By comparing this sequence to 288 control genomes, we identified a private missense variant in the ASPRV1 gene encoding the retroviral-like aspartic protease 1, also known as SASPase, which is involved in the processing of profilaggrin. The variant was due to a de novo mutation event, which is consistent with the patient being an isolated single case of a novel form of ichthyosis. Filaggrin protein expression was altered in the skin of the affected dog. Thus, our results strongly suggest that genetic variants in ASPRV1 can cause ichthyosis by altering filaggrin processing. http://dx.doi.org/10.13039/501100001711 Schweizerischer Nationalfonds zur Frderung der Wissenschaftlichen Forschung CRSII3_160738 / 1 http://orcid.org/0000-0003-0553-4880 Leeb Tosso This study was supported by grants from the Swiss National Science Foundation (CRSII3_160738 / 1) and the Albert-Heim

... obtained whole genome sequences from both parents of the affected dogs. Inspection of the sequencing data for each of the 19 heterozygous candidate variants revealed that only one of them was indeed a de novo variant ( S1 Table ). This de novo variant was a missense variant, c.1052T>C, located in the ASPRV1 gene encoding aspartic peptidase, retroviral-like 1 also known as skin aspartic protease (SASPase), which is involved in profilaggrin-to-filaggrin processing [ 17 , 18 , 22 ]. We performed Sanger sequencing in the affected dog and both parents and confirmed that the variant was absent in both parents ( Fig 3A ). We experimentally confirmed the correct parentage by an analysis of microsatellite and SNV genotypes in the trio. 10.1371/journal.pgen.1006651.g003 Fig 3 Sanger electropherograms of the ASPRV1:c.1052T>C variant and evolutionary conservation of leucine 351 in the ASPRV1 protein. (A) A genomic ASPRV1 fragment was amplified by PCR and sequenced with the Sanger method. The figure shows

infinome is an experiment to study aging. Link your 23andMe account for personalized reports.

Gene: ASPRV1 - aspartic peptidase, retroviral-like 1 - (NCBI)

Images from Open Access Papers

Search Results from Open Access Papers