title: Novel mutation in NIPAL4 in a Romanian family with autosomal recessive congenital ichthyosis.
abstract: Autosomal recessive congenital ichthyosis (ARCI), a severe and highly clinically heterogeneous group of mendelian disorders of cornification, is the result of mutations in at least nine genes regulating the epidermal barrier functionality. NIPAL4 is the second most frequently mutated ARCI gene. We report two adult patients from a nonconsanguineous family of Romanian origin, who had lamellar ichthyosis. A positive in situ transglutaminase 1 activity assay excluded a putative TGM1 mutation. NIPAL4 sequencing revealed in both patients a new homozygous missense mutation, c.403A>C, affecting a highly conserved amino acid (p. Ser135Arg) and predicted to be deleterious according to in silico analysis. In addition to the ARCI features, the patients had caries and partial edentation. Although delay in dental treatment led to caries progression and extraction of secondary teeth, this finding raises the possibility of a deficiency in enamel mineralization due to NIPAL4 dysfunction as an Mg(2+) transporter. Evaluating new patients with ARCI provides fruitful clinical and molecular findings.
authors.affiliation: Dermatology Department, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: D
authors.identifier: http://orcid.org/0000-0002-2118-4027
authors.initials: D
authors.lastname: Maier
authors.affiliation: Service de Dermatologie, Centre de Référence des Maladies Rares de la Peau, Hôpital Larrey, Toulouse, France.|UMR 5165 CNRS-1056 INSERM-Université Toulouse III, 'Différenciation Epidermique et Autoimmunité Rhumatoïde', Hôpital Purpan, Toulouse, France.
authors.forename: J
authors.initials: J
authors.lastname: Mazereeuw-Hautier
authors.affiliation: Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Targu Mures, Romania.
authors.forename: M
authors.initials: M
authors.lastname: Tilinca
authors.affiliation: Dermatology Department, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: R
authors.initials: R
authors.lastname: Cosgarea
authors.affiliation: UMR 5165 CNRS-1056 INSERM-Université Toulouse III, 'Différenciation Epidermique et Autoimmunité Rhumatoïde', Hôpital Purpan, Toulouse, France.
authors.forename: N
authors.initials: N
authors.lastname: Jonca
mesh_terms: D000328:Adult; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C499859:NIPAL4 protein, human; D011956:Receptors, Cell Surface