| Autor: |
Wertheim-Tysarowska K; Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland., Osipowicz K; Department of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, 02-008 Warsaw, Poland., Gielniewski B; Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland., Wojtaś B; Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland., Szabelska-Beręsewicz A; Department of Mathematical and Statistical Methods, Poznań University of Life Sciences, 60-637 Poznań, Poland., Zyprych-Walczak J; Department of Mathematical and Statistical Methods, Poznań University of Life Sciences, 60-637 Poznań, Poland., Mika A; Department of Pharmaceutical Biochemistry, Medical University of Gdansk, 80-211 Gdansk, Poland., Tysarowski A; Molecular and Translational Oncology Department and Cancer Molecular and Genetic Diagnostics Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland., Duk K; Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland., Rygiel AM; Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland., Niepokój K; Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland., Woźniak K; Department of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, 02-008 Warsaw, Poland., Kowalewski C; Department of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, 02-008 Warsaw, Poland., Wierzba J; Department of Paediatrics, Haematology and Oncology, Department of General Nursery, Medical University of Gdansk, 80-211 Gdansk, Poland., Jezela-Stanek A; Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland. |
| Abstrakt: |
Loricrin keratoderma (LK) is a rare autosomal dominant genodermatosis caused by LORICRIN gene mutations. The pathogenesis of the disease is not yet fully understood. So far, only 10 pathogenic variants in LORICRIN 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 LORICRIN 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 LORICRIN 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. |
