853 Hair progenitor cells dictate hair pigmentation through non-cell autonomous KIT signaling

Abstract

Dorman-Chanarin syndrome (DCS) is an autosomal recessive, neutral lipid storage disorder with ichthyosis to loss-of-function mutation in CGI-58, characterized by the presence of intracellular lipid droplets in cells of multiple organs. CGI-58 is an activator of adipose triglyceride lipase (ATGL) contributing to triglyceride (TG) lipolysis. Although dysfunction of CGI-58 is considered to be the primary cause, the pathomechanism of ichthyosis in DCS still remains undefined. Here, we report a case of 72-year-old man with DCS, harboring a novel missense mutation in the exon 3 of CGI-58 gene in one allele, presented ichthyosiform erythroderma with a distinct seasonal variation (J Dermatol Sci 2010; 57: 102). His skin lesions were aggravated in summer but resolved spontaneously during winter. Biochemical analysis of scales from his lesions, revealed increased levels of TG and decreased levels of fatty acids (FA), indicating dysfunction of ATGL. Notably, the patient showed higher levels of TG but lower FA in the scales taken in summer than those in winter, suggesting that 'seasonal' fluctuated activity of ATGL might be associated with the clinical severity (J Dermatol Sci 2010; 57: 102). Strikingly, topical application of menthol containing pasting resulted in local resolution of his ichthyosiform lesions. Furthermore, improvement of water retention capability was observed at the ameliorated lesion by menthol pasting. Since menthol is an agonist of transient receptor potential M8 (TRPM8), which is activated by low temperature below 22 o C. We now speculate that temperature-dependent mechanism may be involved in the etiology of DCS in this specific patient. Our case gives a new piece of puzzle to elucidate the association between lipid metabolism pathway and thermo-regulation in keratinocytes.