Linear epidermal nevus caused by a novel mosaic heterozygous PTPN11 variant

Summary: Abstract Body: Linear epidermal nevus (LEN) is a rare dermatological condition with skin disease distributed along Blaschko’s lines. We present a 3-year-old female case who presented with congenital linear skin lesions on her right side with sharp cutoff at the midline. Physical examination revealed multiple light pink to red papules and hyperkeratotic plaques following Blaschko’s lines. Histopathological examination of the affected skin revealed acanthosis, increased capillaries in the papillary dermis, and sparse lymphocytic inflammation. Unaffected skin showed no significant abnormalities. Whole exome sequencing in the affected tissue revealed a heterozygous missense variant (c.C1361T, p.Pro454Leu) in the PTPN11 gene which was absent in saliva and unaffected cultured keratinocytes. Quantitative RNA in situ hybridization did not reveal any changes in IL-17A, IL-13, and IL-36γ levels. Immunofluorescence staining showed increased phospho-S6 Ribosomal Protein levels in the affected skin in both epidermis and capillaries, suggesting upregulated activity of the RAS/MAPK pathway. CD34 staining which labels vascular endothelial cells, was also significantly elevated in the affected skin. Cell proliferation in the basal epidermis of affected skin was increased compared to unaffected skin (36.9% vs. 7.7% Ki-67+ respectively). Our study provides evidence for phenotypic expansion in linear genetic disorders associated with PTPN11 damaging variants. Xingyuan Jiang¹, Tiffany X. Chen¹, Ronghua Hu¹, Ryland D. Mortlock^{1, 2}, Christine Ko^{1, 3}, Keith Choate^{1, 2, 3} 1. Dermatology, Yale University School of Medicine, New Haven, CT, United States. 2. Genetics, Yale University School of Medicine, New Haven, CT, United States. 3. Pathology, Yale University School of Medicine, New Haven, CT, United States. Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics