2026-04-14T06:41:21Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/119272025-05-03T13:43:40Zcom_2072_378071com_2072_378040col_2072_378097

00925njm 22002777a 4500 dc Glennie, Lorraine author Xunclà, Mar author Gloria, Aparicio author Codina Solà, Marta author TIZZANO, EDUARDO F. author Lasa-Aranzasti, Amaia author Garcia-Arumi, Elena author 2024-09-18T13:56:56Z 2024-09-18T13:56:56Z 2024-07 Hyperkeratosis; Palmoplantar keratoderma Hiperqueratosis; Queratodermia palmoplantar Hiperqueratosi; Queratodermia palmoplantar Palmoplantar keratoderma (PPK) is a multi-faceted skin disorder characterized by the thickening of the epidermis and abrasions on the palms and soles of the feet. Among the genetic causes, biallelic pathogenic variants in the FAM83G gene have been associated with PPK in dogs and humans. Here, a novel homozygous variant (c.794G>C, p.Arg265Pro) in the FAM83G gene, identified by whole exome sequencing in a 60-year-old female patient with PPK, is reported. The patient exhibited alterations in the skin of both hands and feet, dystrophic nails, thin, curly and sparse hair, long upper eyelid eyelashes, and poor dental enamel. FAM83G activates WNT signalling through association with ser/thr protein kinase CK1α. When expressed in FAM83G−/− DLD1 colorectal cancer cells, the FAM83GR265P variant displayed poor stability, a loss of interaction with CK1α and attenuated WNT signalling response. These defects persisted in skin fibroblast cells derived from the patient. Our findings imply that the loss of FAM83G-CK1α interaction and subsequent attenuation of WNT signalling underlie the pathogenesis of PPK caused by the FAM83GR265P variant. G.P.S. was supported by the UKRI Medical Research Council (grant MC_UU_00018/6) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy (Boehringer Ingelheim, GlaxoSmithKline, Merck-Serono). L.G. was supported by MRC PPU PhD studentship. Pell - Malalties - Aspectes genètics Transducció de senyal cel·lular Fibroblasts DISEASES::Skin and Connective Tissue Diseases::Skin Diseases::Keratosis::Skin and Connective Tissue Diseases::Skin Diseases::Keratoderma, Palmoplantar PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Signal Transduction::Wnt Signaling Pathway ANATOMY::Cells::Connective Tissue Cells::Fibroblasts ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades de la piel::queratosis::enfermedades de la piel y tejido conjuntivo::enfermedades de la piel::queratodermia palmoplantar FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::transducción de señales::vía de señalización Wnt ANATOMÍA::células::células del tejido conectivo::fibroblastos A novel FAM83G variant from palmoplantar keratoderma patient disrupts WNT signalling via loss of FAM83G-CK1α interaction