Autosomal recessive congenital ichthyosis (ARCI) is a group of rare monogenic skin disorders affecting the cornification of epidermis. Etiologically, mutations in around 10 genes have been demonstrated so far, with TGM1 being the most commonly affected gene. Most of ARCI genes are involved in the metabolic pathway of acylceramide, the key lipid for skin barrier function. Transglutaminase 1 encoded by TGM1 covalently bind acylceramide to the corneocyte protein envelope to form corneocyte lipid envelop (CLE) that is a crucial structure for skin barrier function. 

Yet, the impact of TGM1 mutations on the expression of other ARCI causing genes remains elusive. Therefore, we performed oligoarray analysis with 4 healthy controls and 5 patients with TGM1 mutations, 4 of which were born as collodion babies. In total, 1221 transcripts were differentially expressed (Benjamini adjusted p<0.05) in the patients compared to controls. The differentially expressed genes were enriched in several important biological networks, such as epidermal keratinocyte differentiation, lipid processing oxidoreductase, CLE, and immunity. 

In particularly, the expression of 8 other ichthyosis-causing genes (including syndromic forms), were upregulated to variable extents. Moreover, the results were partially verified by qPCR and immunofluorescence staining. This suggests that there is a compensatory mechanism elicited in TGm-1 deficient epidermis striving to restore the skin lipid barrier by producing more acylceramide.

Ichthyosis patients with TGM1 mutations show aberrant transcriptomic expression