X-linked ichthyosis (XLI) is after ichthyosis vulgaris (IV) the most frequent occurring genetic skin scaling disease (1 in 6,000). The disorder results from steroid sulfatase deficiency due to defects in the STS gene. Most patients (90%) have a genomic deletion encompassing the entire gene. Clinical distinction between XLI and IV may be difficult. Moreover, the incidence of FLG mutations causal to IV is high (5%) and therefore co-inheritance with STS mutations may occur, modifying the phenotype. Genetic analysis was performed of STS in patients clinically diagnosed with XLI and in most of them subsequent analysis of FLG or whole exome sequencing (WES) was done, to determine the spectrum of mutations and improve diagnoses. Blood samples from 109 Dutch patients suspected having XLI were analyzed for the STS gene using MLPA and Sanger sequencing. Additionally, 63 samples were tested for FLG with smMIP-NGS analysis and 3 with WES. In 71 of 109 patients (65%) the STS gene was affected, of whom 57 involved an STS deletion (80%), which is comparable with previous cohort studies. The other 14 STS mutations are novel (n=11), adding 14% to the existing STS mutation database. From the 63 patients (58%) also tested for FLG, 23 patients (21% of total cohort) had FLG mutations of whom 4 in concomitant with an STS mutation. In 3 patients, mutations were identified in genes associated with autosomal recessive congenital ichthyosis (ARCI). Part of the clinically diagnosed XLI patients are in fact IV (17%) or ARCI patients (3%), indicating the difficult distinction between the ichthyosis diseases. The phenotype of 4 XLI patients may be modified by FLG mutations, certifying DNA analysis of both genes to facilitate accurate diagnostic confirmation.

ESDR182 - Genetic heterogeneity of STS gene mutations in a Dutch patient cohort clinically suspected for X-linked recessive ichthyosis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING