409 Epigenetic regulation of alopecia areata

Abstract

Becker's nevus is a common cutaneous disorder with unknown pathogenesis, affecting between 1 in 200 to 1 in 50 individuals. Affected individuals typically develop a hyperpigmented overgrowth of hair and tissue on their torso or upper extremities during adolescence which can be distressing. In some cases, Becker's nevi can be associated with underlying ipsilateral muscle hypoplasia or other extracutaneous abnormalities, termed Becker's nevus syndrome. Whole-exome, Sanger, and CRISPR site-specific sequencing identified recurrent hotspot mutations in the cytoplasmic beta-actin encoding gene ACTB (p.R147C, p.R147S) in 14/24, or 58% of Becker's nevi that was absent from adjacent non-lesional skin tissue. Interestingly, the ACTB mutation was also detected in an individual with Becker's nevus syndrome with unilateral delayed breast development. Laser capture microdissection of Becker's nevi revealed the mutation occurred solely in the smooth muscle bundles of the skin. Functional analysis of the ACTB mutations in myocytes showed that this mutation did not affect F-actin stability, nor increased signaling activity of the RAS or Hedgehog signaling pathways as measured by phospo-Erk and Gli1 respectively. Further investigation into the novel role of postzygotic ACTB mutations in Becker's nevi is recommended.