Fibroblast apoptosis in a patient affected by lamellar ichthyosis

Lamellar ichthyosis (LI) is a congenital recessive skin disorder characterized by generalized scaling and hyperkeratosis. The pathology may be caused by mutations in transglutaminase 1 (TGM1) gene that encodes an enzyme critical for terminally differentiating keratinocytes. Because of evidences that transglutaminase enzymes are involved in programmed cell death, we investigated morphological and biochemical apoptotic parameters in cultured skin fibroblasts from a patient with a severe LI and homozygous for the TGM1 R142H mutation. The principle apoptotic signals (mitochondrial membrane potential, analysis of oxygen consumption, DNA fragmentation and Bax/Bcl-2 gene expression) were analyzed in cultured fibroblasts from a LI patient, his mother (TGM1 mutation carrier) and a control subject. LI fibroblasts showing a reduction of fibronectin expression evidenced a strong inhibition of oxygen consumption, a dramatic drop in the mitochondrial membrane potential (Delta psi(m)), and a higher apoptotic index. The present results suggest a possible connection between the alterations in the keratinization process leading to LI and the observed increased fibroblast apoptosis