Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A.

The Journal of Investigative Dermatology
Janan MohamadEli Sprecher

Abstract

Peeling skin syndromes form a large and heterogeneous group of inherited disorders characterized by superficial detachment of the epidermal cornified cell layers, often associated with inflammatory features. Here we report on a consanguineous family featuring noninflammatory peeling of the skin exacerbated by exposure to heat and mechanical stress. Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the disease phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis. Filaggrin 2 was found to be expressed throughout the cornified cell layers and to colocalize with corneodesmosin that plays a crucial role in maintaining cell-cell adhesion in this region of the epidermis. The absence of filaggrin 2 in the patient skin was associated with markedly decreased corneodesmosin expression, which may contribute to the peeling phenotype displayed by the patients. Accordingly, using the dispase dissociation assay, we showed that FLG2 downregulation interferes with keratinocyte cell-cell adhesion. Of particular interest, this effect was aggravated by temperature elevation, co...Continue Reading

Citations

Jan 19, 2019·Clinical and Experimental Dermatology·J MohamadE Sprecher
Oct 3, 2020·Computational and Structural Biotechnology Journal·Tom Rabinowitz, Noam Shomron
Jan 30, 2021·Computational and Structural Biotechnology Journal·Tom RabinowitzNoam Shomron
Apr 6, 2020·The Journal of Investigative Dermatology·Janan MohamadEli Sprecher
Mar 4, 2021·Biomedicines·Dragan CopicMichael Mildner
Nov 17, 2020·The Journal of Investigative Dermatology·Satomi IgawaAnna Di Nardo
Sep 14, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rachel BaurStacey E Anderson

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