Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis

Ital J Pediatr. 2022 Aug 13;48(1):145. doi: 10.1186/s13052-022-01336-0.


Background: Congenital ichthyosis (CI) is a heterogeneous group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, often associated to erythroderma. They are rare diseases, with overall incidence of 6.7 in 100,000. Clinical manifestations are due to mutations in genes mostly involved in skin barrier formation. Based on clinical presentation, CI is distinguished in non-syndromic and syndromic forms. To date, mutations of more than 50 genes have been associated to different types of CI.

Cases presentation: We report on three Italian unrelated newborns showing clinical signs compatible with different forms of CI of variable severity, namely Harlequin ichtyosis (HI), epidermolytic ichtyosis (EI) and autosomal recessive ichtyosis with hypotrichosis (ARIH). Target next generation sequencing (NGS) analysis identified three novel mutations of the ABCA12, KRT1 and ST14 genes, respectively associated to such congenital ichtyoses, not reported in literature. Genomic investigation allowed to provide the more appropriate management to each patient, based on an individualized approach.

Conclusions: Our report highlights the wide genetic heterogeneity and phenotypic variability of CI. It expands the current knowledge on such diseases, widening their genomic database, and providing a better clinical characterization. Furthermore, it underlines the clinical relevance of NGS, which is essential to address the management of patients. Indeed, it may guide towards the most adequate approach, preventing clinical obstinacy for subjects with more severe forms and unfavorable outcomes (together with the support, in such situations, of bioethicists included within the multidisciplinary care team), as well as reassuring families in those with milder course and favorable evolution.

Keywords: Autosomal recessive ichtyosis with hypotrichosis; Case report; Congenital ichthyosis; Epidermolytic ichtyosis; Harlequin ichtyosis; Target NGS.

MeSH terms

  • ATP-Binding Cassette Transporters
  • Alopecia / congenital
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Ichthyosis, Lamellar* / diagnosis
  • Ichthyosis, Lamellar* / genetics
  • Infant, Newborn
  • Keratin-1 / genetics
  • Mutation
  • Serine Endopeptidases / genetics*


  • ABCA12 protein, human
  • ATP-Binding Cassette Transporters
  • KRT1 protein, human
  • Keratin-1
  • Serine Endopeptidases
  • ST14 protein, human

Supplementary concepts

  • Total Hypotrichosis, Mari type