Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis—Like Autosomal Recessive Congenital Ichthyosis

Erythrokeratodermia variabilis (EKV) is a rare disorder of cornification usually associated with dominant mutations in the GJB3 and GJB4 genes encoding connexins (Cx)31 and 30.3. Genetic heterogeneity of EKV has already been suggested. We investigated at the clinical and genetic level a consanguineous Tunisian family with 2 sisters presenting an autosomal recessive form of EKV to better characterize this disease. Mutational analysis initially screened the connexin genes and Whole-exome sequencing (WES) was performed to identify the molecular aetiology of the particular EKV phenotype in the proband. Migratory shaped erythematous areas are the initial presenting sign followed by relatively stable hyperkeratotic plaques are the two predominates characteristics in both patients. However, remarkable variability of morphological and dominating features of the disease were observed between patients. In particular, the younger sister (proband) exhibited ichthyosiform-like appearance suggesting Autosomal Recessive Congenital Ichthyosis (ARCI) condition. No causative mutations were detected in the GJB3 and GJB4 genes. WES results revealed a novel missense homozygous mutation in NIPAL4 gene (c.835C>G, p.Pro279Ala) in both patients. This variant is predicted to be likely pathogenic. In addition, in silico analysis of the mutated 3D domain structure predicted that this variant would result in NIPA4 protein destabilization and Mg2+ transport perturbation, pointing out the potential role of NIPAL4 gene in the development and maintenance of the barrier function of the epidermis. Taken togheter, these results expand the clinical phenotype associated with NIPAL4 mutation and reinforce our hypothesis of NIPAL4 as the main candidate gene for the EKV-like ARCI phenotype.

Peeling skin syndrome: an investigational dilemma

<p><span lang="EN-IN">Peeling skin syndrome is a rare autosomal recessive disorder of cornification that starts either at birth or later in childhood, characterized by widespread painless peeling of the skin in superficial sheets. We report the case of a 13-year-old boy who presented with asymptomatic peeling of skin since birth. Sheets of skin were peeling from the neck, trunk and extremities following mild friction or rubbing, with sparing of palms and soles. The case is being reported due to its rarity.</span></p>

Progressive symmetric eritrocarotodermia Gottron: A rare case

The article deals with ethiopathogenetic factors of origin of progredient symmetric erythrokeratodermia of Gottron which is mainly characterized by autosomal dominant mode of inheritance and is classified as a disorder of cornification with extra epidermal cellular proliferation.Clinicopathologic criteria on the basis of which this pathology can be verified are described here, such as: onset of a disease at an early age, strictly divided polycyclic, fixed, hyperkeratotic plaques with a narrow erythematic crown and a clean-cut, sometimes hyper pigmented edge, which are symmetrically located on skin on head, buttocks, limbs and are not prone to quick peripheral growth; large frequency of palmoplantar keratoderma and also histological changes typical of erythrokeratodermia.The article describes a rare clinical case of autosomal-recessive progredient symmetric erythrokeratodermia of Gottron which is distinguished by seasonal changes of skin pathological process — emergence of rash in winter and complete remissions in summer.