Genetical, clinical and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4.

Fiche publication

Date publication

juillet 2019

Journal

Human mutation

Auteurs

Membres identifiés du Cancéropôle Est :
Pr VABRES Pierre

Tous les auteurs :
Ballin N, Hotz A, Bourrat E, Küsel J, Oji V, Bouadjar B, Brognoli D, Hickman G, Heinz L, Vabres P, Marrakchi S, Leclerc-Mercier S, Irvine A, Tadini G, Hamm H, Has C, Blume-Peytavi U, Mitter D, Reitenbach M, Hausser I, Zimmer AD, Alter S, Fischer J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31347739

Résumé

Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, ten genes have been identified to be causative for ARCI. NIPAL4 (Nipa-Like Domain-Containing 4) is the second most commonly mutated gene in ARCI. In this study we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, potential hot spot for mutations and genotype-phenotype correlations. This article is protected by copyright. All rights reserved.