The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology
Loricrin keratoderma (LK) is a rare autosomal dominant genodermatosis caused by <i>LORICRIN</i> gene mutations. The pathogenesis of the disease is not yet fully understood. So far, only 10 pathogenic variants in <i>LORICRIN</i> have been described, with all of them but one be...
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2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9459 |
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| author | Katarzyna Wertheim-Tysarowska Katarzyna Osipowicz Bartłomiej Gielniewski Bartosz Wojtaś Alicja Szabelska-Beręsewicz Joanna Zyprych-Walczak Adriana Mika Andrzej Tysarowski Katarzyna Duk Agnieszka Magdalena Rygiel Katarzyna Niepokój Katarzyna Woźniak Cezary Kowalewski Jolanta Wierzba Aleksandra Jezela-Stanek |
| author_facet | Katarzyna Wertheim-Tysarowska Katarzyna Osipowicz Bartłomiej Gielniewski Bartosz Wojtaś Alicja Szabelska-Beręsewicz Joanna Zyprych-Walczak Adriana Mika Andrzej Tysarowski Katarzyna Duk Agnieszka Magdalena Rygiel Katarzyna Niepokój Katarzyna Woźniak Cezary Kowalewski Jolanta Wierzba Aleksandra Jezela-Stanek |
| author_sort | Katarzyna Wertheim-Tysarowska |
| collection | DOAJ |
| description | Loricrin keratoderma (LK) is a rare autosomal dominant genodermatosis caused by <i>LORICRIN</i> gene mutations. The pathogenesis of the disease is not yet fully understood. So far, only 10 pathogenic variants in <i>LORICRIN</i> have been described, with all of them but one being deletions or insertions. The significance of rare nonsense variants remains unclear. Furthermore, no data regarding the RNA expression in affected patients are available. The aim of this study is to describe the two variants in the <i>LORICRIN</i> gene found in two distinct families: the novel pathogenic variant c.639_642dup and a rare c.10C > T (p.Gln4Ter) of unknown significance. We also present the results of the transcriptome analysis of the lesional loricrin keratoderma epidermis of a patient with c.639_642dup. We show that in the LK lesion, the genes associated with epidermis development and keratocyte differentiation are upregulated, while genes engaged in cell adhesion, differentiation developmental processes, ion homeostasis and transport, signaling and cell communication are downregulated. In the context of the p.Gln4Ter clinical significance evaluation, we provide data indicating that <i>LORICRIN</i> haploinsufficiency has no skin consequences. Our results give further insight into the pathogenesis of LK, which may have therapeutic implications in the future and important significance in the context of genetic counseling. |
| first_indexed | 2024-03-11T03:05:45Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:05:45Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-80ddb96cbb854d26996472ff6ff7563e2023-11-18T07:59:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411945910.3390/ijms24119459The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma PathologyKatarzyna Wertheim-Tysarowska0Katarzyna Osipowicz1Bartłomiej Gielniewski2Bartosz Wojtaś3Alicja Szabelska-Beręsewicz4Joanna Zyprych-Walczak5Adriana Mika6Andrzej Tysarowski7Katarzyna Duk8Agnieszka Magdalena Rygiel9Katarzyna Niepokój10Katarzyna Woźniak11Cezary Kowalewski12Jolanta Wierzba13Aleksandra Jezela-Stanek14Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, PolandDepartment of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, 02-008 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, PolandDepartment of Mathematical and Statistical Methods, Poznań University of Life Sciences, 60-637 Poznań, PolandDepartment of Mathematical and Statistical Methods, Poznań University of Life Sciences, 60-637 Poznań, PolandDepartment of Pharmaceutical Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandMolecular and Translational Oncology Department and Cancer Molecular and Genetic Diagnostics Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, PolandDepartment of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, PolandDepartment of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, PolandDepartment of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, 02-008 Warsaw, PolandDepartment of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, 02-008 Warsaw, PolandDepartment of Paediatrics, Haematology and Oncology, Department of General Nursery, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandLoricrin keratoderma (LK) is a rare autosomal dominant genodermatosis caused by <i>LORICRIN</i> gene mutations. The pathogenesis of the disease is not yet fully understood. So far, only 10 pathogenic variants in <i>LORICRIN</i> have been described, with all of them but one being deletions or insertions. The significance of rare nonsense variants remains unclear. Furthermore, no data regarding the RNA expression in affected patients are available. The aim of this study is to describe the two variants in the <i>LORICRIN</i> gene found in two distinct families: the novel pathogenic variant c.639_642dup and a rare c.10C > T (p.Gln4Ter) of unknown significance. We also present the results of the transcriptome analysis of the lesional loricrin keratoderma epidermis of a patient with c.639_642dup. We show that in the LK lesion, the genes associated with epidermis development and keratocyte differentiation are upregulated, while genes engaged in cell adhesion, differentiation developmental processes, ion homeostasis and transport, signaling and cell communication are downregulated. In the context of the p.Gln4Ter clinical significance evaluation, we provide data indicating that <i>LORICRIN</i> haploinsufficiency has no skin consequences. Our results give further insight into the pathogenesis of LK, which may have therapeutic implications in the future and important significance in the context of genetic counseling.https://www.mdpi.com/1422-0067/24/11/9459loricrinloricrin keratodermatranscriptomemutation |
| spellingShingle | Katarzyna Wertheim-Tysarowska Katarzyna Osipowicz Bartłomiej Gielniewski Bartosz Wojtaś Alicja Szabelska-Beręsewicz Joanna Zyprych-Walczak Adriana Mika Andrzej Tysarowski Katarzyna Duk Agnieszka Magdalena Rygiel Katarzyna Niepokój Katarzyna Woźniak Cezary Kowalewski Jolanta Wierzba Aleksandra Jezela-Stanek The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology International Journal of Molecular Sciences loricrin loricrin keratoderma transcriptome mutation |
| title | The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology |
| title_full | The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology |
| title_fullStr | The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology |
| title_full_unstemmed | The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology |
| title_short | The Epidermal Transcriptome Analysis of a Novel c.639_642dup <i>LORICRIN</i> Variant-Delineation of the Loricrin Keratoderma Pathology |
| title_sort | epidermal transcriptome analysis of a novel c 639 642dup i loricrin i variant delineation of the loricrin keratoderma pathology |
| topic | loricrin loricrin keratoderma transcriptome mutation |
| url | https://www.mdpi.com/1422-0067/24/11/9459 |
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