Predictive phenotyping of inherited ichthyosis by next‐generation DNA sequencing

Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature

“…Disrupted terminal differentiation, lipid homeostasis, increased TEWL, and associations with atopy have historically linked ichthyoses to AD. 2,3,18,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]43,[50][51][52][83][84][85][86] However, our recent profiling of ichthyotic skin using a limited geneexpression approach demonstrated enhanced T H 17/IL-23 response with marginal T H 2 skewing and lack of abnormalities in 3 differentiation proteins (FLG, LOR, and PPL), aligning it more closely to the psoriasis profile. 53 The present study is the first comprehensive genomic skin fingerprinting of the most common orphan ichthyosis subtypes to J ALLERGY CLIN IMMUNOL VOLUME 143, NUMBER 2 FIG 5.…”

“…[18][19][20][21][22][23][24][25][26] Human skin and blood studies have been limited to a few patients or select ichthyosis subtypes and have shown abnormalities in lipid, cornified envelope (CE), and/or other differentiation measures. 18,[27][28][29][30][31][32][33][34][35][36][37][38][39][40] Several observations link ichthyoses, particularly Netherton syndrome (NS), to atopic dermatitis (AD), which is marked by epidermal barrier defects and immune dysregulation. 41 NS shares the eosinophilia and increased T H 2/atopy-related markers (thymic stromal lymphopoietin [TSLP], chemokine like 17 [CCL17]/ thymus and activation-regulated chemokine, and IgE) of AD, 18,20,[42][43][44][45][46][47][48][49] and polymorphisms of serine protease inhibitor, Kazal-type 5 (mutated in patients with NS) are associated with AD.…”

Whole‐exome sequencing for diagnosis of hereditary ichthyosis

“…Furthermore, the high number of responsible disease-causing genes identified in our case series underlines the genetic heterogeneity of ichthyosis and reflects the frequently demanding bedside evaluation. 4 WES exhibits great potential in disclosing the molecular diagnosis, regardless of clinical presentation, exemplified by four patients having their initial diagnosis changed or specified following WES analysis.…”

“…More than 40 genes have been shown to cause ichthyosis . Establishing a correct diagnosis based on clinical, histopathological and electron microscopy evaluation may be challenging and does not establish the molecular cause of the disease …”

“…[1][2][3] Establishing a correct diagnosis based on clinical, histopathological and electron microscopy evaluation may be challenging and does not establish the molecular cause of the disease. 4 Identification of the molecular cause of congenital ichthyosis is of clinical, as well as theoretical, importance for a number of reasons, including the following: (a) A molecular cause may provide important information about prognosis and need for medical follow-up. (b) Genetic subgroups of patients might be particularly responsive or resistant to conventional treatment, reflecting the path to individualized medicine.…”