Autosomal recessive congenital ichthyosis: CERS3 mutations identified by a next generation sequencing panel targeting ichthyosis genes

Abstract

There are at least 38 mutant genes known to be associated with the ichthyosis phenotypes, and autosomal recessive congenital ichthyosis (ARCI) is a specific subgroup caused by mutations in 13 different genes. Mutations in some of these genes, such as CERS3 with only two previous reports, are rare. In this study, we identified mutations in candidate genes in consanguineous families with ARCI with a next generation sequencing (NGS) array that incorporates 38 ichthyosis associated genes. We applied this sequencing array to DNA from 140 ichthyosis families with high prevalence of consanguinity. Among these patients we identified six distinct, previously unreported mutations in CERS3 in six Iranian families. These mutations in each family co-segregated with the ichthyosis phenotype. The patients demonstrated collodion membrane at birth, acrogeria, generalized scaling, and hyperlinearity of the palms and soles. The presence of a significant percentage of CERS3 mutations in our cohort depicts a marked difference between the etiology of ichthyoses in genetically poorly characterized regions and well-characterized western populations. Also, it shows that rare alleles are more prevalent in the gene pool of consanguineous populations and emphasizes the importance of these population studies for better understanding of ichthyosis pathogenesis.

Autosomal recessive congenital ichthyosis: Genomic landscape and phenotypic spectrum in a cohort of 125 consanguineous families

“…Interestingly, among these 106 diagnosed ARCI families, 25 families had mutations in PNPLA1 or CERS3 . We previously reported 19 families including six CERS3 and 13 PNPLA1 families out of these 125 families (Vahidnezhad et al., ; Youssefian et al., ; see Supporting Information Table S1). Here, we report an additional six mutations in PNPLA1 gene, five of them being novel.…”

Genotype–phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis

“…However, ABCA12 mutations may also have a phenotype with dark scale or a milder CIE appearance . Recent reports in rarer forms of ARCI with CERS3 , PNPLA1 and ST14 mutations have shown great variability in phenotype …”

Congenital ichthyosis in Prader–Willi syndrome associated with maternal chromosome 15 uniparental disomy: Case report and review of autosomal recessive conditions unmasked by UPD

“…To the best of our knowledge this is only the third CERS3 truncating variant reported, and the 16th family reported with CERS3 congenital ichthyosis. We have summarized the previously reported cases genotype and phenotype data in Table S2 (Eckl et al, 2013;Polubothu et al, 2018;Radner et al, 2013;Youssefian et al, 2017Youssefian et al, , 2019. Of 11 variants reported (including this proband), five are missense variants, three are nonsense, one is a deletion-insertion, one a splice variant, and one a more complex deletion impacting exon 13 and the 3 0 UTR of CERS3 ( Figure S2 and Table S2).…”