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

• Published in: Italian journal of pediatrics 2022-08, Vol.48 (1), p.1-145, Article 145
• Main Authors: Serra, Gregorio, Memo, Luigi, Cavicchioli, Paola, Cutrone, Mario, Giuffrè, Mario, La Torre, Maria Laura, Schierz, Ingrid Anne Mandy, Corsello, Giovanni
• Format: Article
• Language: English
• Subjects: Antibiotics; Autosomal recessive ichtyosis with hypotrichosis; Case Report; Catheters; Congenital diseases; Congenital ichthyosis; Edema; Epidermolytic ichtyosis; Family medical history; Genes; Genetic disorders; Genetic variability; Genomics; Harlequin ichtyosis; Ichthyosis; Laboratories; Mutation; Neonates; Next-generation sequencing; Parents & parenting; Patients; Pregnancy; Premature birth; Proteins; Sepsis; Target NGS; Vagina; Ventilation; Ventilators
• ISSN: 1824-7288; 1720-8424; 1824-7288
• 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.