A variant in the gene in a dog with ichthyosis
The skin undergoes a constant process of self-renewing and keratinocytes migrate from the basal layer of the epidermis to the uppermost layer, the stratum corneum, as they differentiate. A defect in the differentiation of keratinocytes can lead to cornification disorders such as ichthyosis. The most common form of this disorder in humans is ichthyosis vulgaris caused by variants in the filaggrin gene. Filaggrin is required for bundling intermediate filaments resulting in the flattening of keratinocytes. Filaggrin is produced from profilaggrin and the processing steps involve 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.
Vyšlo v časopise:
A variant in the gene in a dog with ichthyosis. PLoS Genet 13(3): e32767. doi:10.1371/journal.pgen.1006651
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1006651
Souhrn
The skin undergoes a constant process of self-renewing and keratinocytes migrate from the basal layer of the epidermis to the uppermost layer, the stratum corneum, as they differentiate. A defect in the differentiation of keratinocytes can lead to cornification disorders such as ichthyosis. The most common form of this disorder in humans is ichthyosis vulgaris caused by variants in the filaggrin gene. Filaggrin is required for bundling intermediate filaments resulting in the flattening of keratinocytes. Filaggrin is produced from profilaggrin and the processing steps involve 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.
Zdroje
1. Takeichi T, Akiyama M (2016) Inherited ichthyosis: Non-syndromic forms. J Dermatol 43: 242–251. doi: 10.1111/1346-8138.13243 26945532
2. Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, et al. (2010) Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermat 63: 607–641.
3. Wells RS, Kerr CB (1966) Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. Br Med J 1: 947–950. 20790920
4. Smith FJ, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, et al. (2006) Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 38: 337–342. doi: 10.1038/ng1743 16444271
5. Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6: 328–340. doi: 10.1038/nrm1619 15803139
6. Dale BA, Resing KA, Lonsdale-Eccles JD (1985) Filaggrin: a keratin filament associated protein. Ann New York Acad Sci 455: 330–342.
7. Presland RB, Haydock PV, Fleckman P, Nirunsuksiri W, Dale BA (1992) Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. J Biol Chem 267: 23772–23781. 1429717
8. Hoste E, Kemperman P, Devos M, Denecker G, Kezic S, Yau N, et al. (2011) Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin. J Invest Dermatol 131: 2233–2241. doi: 10.1038/jid.2011.153 21654840
9. Basler E, Grompe M, Parenti G, Yates J, Ballabio A (1992) Identification of point mutations in the steroid sulfatase gene of three patients with X-linked ichthyosis. Am J Hum Genet 50: 483–491. 1539590
10. Lemke JR, Kernland-Lang K, Hörtnagel K, Itin P (2014) Monogenic human skin disorders. Dermatol 229:55–64.
11. Grall A, Guaguere E, Planchais S, Grond S, Bourrat E, Hausser I, et al. (2012) PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet 44: 140–147. doi: 10.1038/ng.1056 22246504
12. Tamamoto-Mochizuki C, Banovic F, Bizikova P, Laprais A, Linder KE, Olivry T (2016) Autosomal recessive congenital ichthyosis due to PNPLA1 mutation in a golden retriever-poodle cross-bred dog and the effect of topical therapy. Vet Dermatol 27: 306–e75. doi: 10.1111/vde.12323 27237723
13. Credille KM, Barnhart KF, Minor JS, Dunstan RW (2005) Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier dogs. Br J Dermatol 153: 51–58. doi: 10.1111/j.1365-2133.2005.06735.x 16029326
14. Mauldin EA, Wang P, Evans E, Cantner CA, Ferracone JD, Credille KM et al. (2015) Autosomal recessive congenital ichthyosis in American Bulldogs is associated with NIPAL4 (ICHTHYIN) deficiency. Vet Pathol 52: 654–662. doi: 10.1177/0300985814551425 25322746
15. Credille KM, Minor JS, Barnhart KF, Lee E, Cox ML, Tucker KA, et al. (2009) Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs. Br J Dermatol 161: 265–272. doi: 10.1111/j.1365-2133.2009.09161.x 19438474
16. Mauldin EA (2013) Canine ichthyosis and related disorders of cornification. Vet Clin North Am Small Anim Pract 43: 89–97. doi: 10.1016/j.cvsm.2012.09.005 23182326
17. Bernard D, Mehul B, Thomas-Collignon A, Delattre C, Donovan M, Schmidt R (2005) Identification and characterization of a novel retroviral-like aspartic protease specifically expressed in human epidermis. J Invest Dermatol 125: 278–287. doi: 10.1111/j.0022-202X.2005.23816.x 16098038
18. Matsui T, Kinoshita-Ida Y, Hayashi-Kisumi F, Hata M, Matsubara K, Chiba M, et al. (2006) Mouse homologue of skin-specific retroviral-like aspartic protease involved in wrinkle formation. J Biol Chem 281: 27512–27525. doi: 10.1074/jbc.M603559200 16837463
19. Besenbacher S, Liu S, Izarzugaza JM, Grove J, Belling K, Bork-Jensen J, et al. (2015) Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios. Nat Comm 6: 5969.
20. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, et al. (2012) Rate of de novo mutations and the importance of father's age to disease risk. Nature 488: 471–475. doi: 10.1038/nature11396 22914163
21. Harland C, Charlier C, Karim L, Cambisano N, Deckers M, Mullaart E, et al. (2016) Frequency of mosaicism points towards mutation-prone early cleavage cell divisions. bioRxiv.
22. Matsuda A, Kosugi S (1997) A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. J Clin Endocrinol Metab 82: 3966–3971. doi: 10.1210/jcem.82.12.4425 9398697
23. Matsui T, Miyamoto K, Kubo A, Kawasaki H, Ebihara T, Hata K, et al. (2011) SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing. EMBO Mol Med 3: 320–333. doi: 10.1002/emmm.201100140 21542132
24. Rhiemeier V, Breitenbach U, Richter KH, Gebhardt C, Vogt I, Hartenstein B, et al. (2006) A novel aspartic proteinase-like gene expressed in stratified epithelia and squamous cell carcinoma of the skin. Am J Pathol 168: 1354–1364. doi: 10.2353/ajpath.2006.050871 16565508
25. Hildenbrand M, Rhiemeier V, Hartenstein B, Lahrmann B, Grabe N, Angel P, et al. (2010) Impaired skin regeneration and remodeling after cutaneous injury and chemically induced hyperplasia in taps-transgenic mice. J Invest Dermatol 130: 1922–1930. doi: 10.1038/jid.2010.54 20237492
26. Sandilands A, Brown SJ, Goh CS, Pohler E, Wilson NJ, Campbell LE, et al. (2012) Mutations in the SASPase gene (ASPRV1) are not associated with atopic eczema or clinically dry skin. J Invest Dermatol 132: 1507–1510. doi: 10.1038/jid.2011.479 22318384
27. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559–575. doi: 10.1086/519795 17701901
28. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760. doi: 10.1093/bioinformatics/btp324 19451168
29. Li H (2011) A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 27: 2987–2993. doi: 10.1093/bioinformatics/btr509 21903627
30. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297–1303. doi: 10.1101/gr.107524.110 20644199
31. Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, et al. (2013) From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinformatics 43:11.0.1–33.
32. Cingolani P, Platts A, Wang le L, Coon M, Nguyen T, Wang L, et al. (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 6: 80–92. doi: 10.4161/fly.19695 22728672
33. Thorvaldsdottir H, Robinson JT, Mesirov JP (2013) Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 14: 178–192. doi: 10.1093/bib/bbs017 22517427
34. Bai B, Zhao WM, Tang BX, Wang YQ, Wang L, Zhang Z, et al. (2015) DoGSD: the dog and wolf genome SNP database. Nucleic Acids Res 43 (Database issue): D777–783. doi: 10.1093/nar/gku1174 25404132
35. Chervet L, Galichet A, McLean WH, Chen H, Suter MM, Roosje PJ, et al. (2010) Missing C-terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis. Exp Dermatol. 19: e343–346. doi: 10.1111/j.1600-0625.2010.01109.x 20626465
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2017 Číslo 3
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy
- A rare loss-of-function mutation reduces blood eosinophil counts and protects from asthma
- A variant in the gene in a dog with ichthyosis
- Fishing for adaptive epistasis using mitonuclear interactions