Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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 Mg 2+ 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 EKVlike ARCI phenotype.
Document type :
Journal articles
Complete list of metadata

https://hal-riip.archives-ouvertes.fr/pasteur-03541087
Contributor : AbdelHakim Ben Hassine Connect in order to contact the contributor
Submitted on : Monday, January 24, 2022 - 1:55:28 PM
Last modification on : Monday, January 24, 2022 - 6:20:40 PM
Long-term archiving on: : Monday, April 25, 2022 - 7:12:05 PM

File

journal.pone.0258777.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Cherine Charfeddine, Nadia Laroussi, Rahma Mkaouar, Raja Jouini, Olfa Khayat, et al.. Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis—Like Autosomal Recessive Congenital Ichthyosis. PLoS ONE, Public Library of Science, 2021, 16 (10), pp.e0258777. ⟨10.1371/journal.pone.0258777⟩. ⟨pasteur-03541087⟩

Share

Metrics

Record views

7

Files downloads

6