Pathogenic Variants in the ABCA12 Gene Associated to Autosomal Recessive Congenital Ichthyosis: Report of an Attenuated Phenotype

Congenital ichthyosis represents keratinisation disorders characterised by abnormal skin scaling across the entire body, leading to a red, denuded, and scaly appearance. A subgroup of this is the autosomal recessive congenital ichthyosis (ARCI), characterised by a severe phenotype and classified according to the molecular mechanisms that underlie the disease. This article reports on the cases of two female patients with symptoms of palmoplantar keratoderma since birth and a variant in the ABCA12 gene that encodes an amino acid glucosylceramide transporter known as ABCA12. The primary role of ABCA12 is to facilitate the transport of molecules across cell and intracellular membranes. Variants involve large deletions and nonsense variants, resulting in a truncated protein that contributes to the severity of harlequin ichthyosis. However, the patients reported in this article present an attenuated phenotype with palmoplantar keratoderma. The subdued presentation in these patients might be elucidated by their compound heterozygous status.