<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Introduction:</bold> Autosomal recessive congenital ichthyosis is a non-syndromic ichthyosis, with a genetic background of mutations in 9 genes. This case series presents clinical and paraclinical particularities of 3 Romanian ARCI patients with NIPAL4 mutation c.527C>A.<bold>Material and methods:</bold> Three Caucasian patients were investigated, two sisters and an unrelated female patient, aged 47, 49, and 42 respectively. Skin anomalies were recorded and documented photographically; peripheral blood samples were harvested for DNA extraction and gene analysis. Skin biopsies were used for histological assessment, electron microscopy, and evaluation of in situ transglutaminase 1 activity.<bold>Results:</bold> All patients presented with generalized ichthyosis, palmoplantar keratoderma, normal hair shafts, and significant oral manifestations. Natural evolution was relatively stable in all cases, without phenotype changing. Medical treatment with retinoids in patients 1 and 2 resulted in normalisation of the skin condition.Histological samples showed hyperkeratosis, acanthosisand perivascular inflammatory infiltrates in the dermis. Positive findings of transglutaminase 1 in situ activity excluded TGM1 deficiency. Direct sequencing of amplicons revealed one homozygous mutation in exon 4, a c.527C>A missense mutation.<bold>Conclusions:</bold> This is the first report of the hotspot mutation NIPAL4 c.527C>A in Romanian autosomal recessive congenital ichthyosis patients. The phenotype was similar to that reported in the literature, while transglutaminase 1 activity in situ assay detected differences in enzyme distribution between patients bearing the same mutation but different phenotypes. Based on the current data, NIPAL4 mutations are more frequent than TGM1 mutations in Romanian patients with autosomal recessive congenital ichthyosis.</abstract>

Introduction: Autosomal recessive congenital ichthyosis is a non-syndromic ichthyosis, with a genetic background of mutations in 9 genes. This case series presents clinical and paraclinical particularities of 3 Romanian ARCI patients with NIPAL4 mutation c.527C>A.Material and methods: Three Caucasian patients were investigated, two sisters and an unrelated female patient, aged 47, 49, and 42 respectively. Skin anomalies were recorded and documented photographically; peripheral blood samples were harvested for DNA extraction and gene analysis. Skin biopsies were used for histological assessment, electron microscopy, and evaluation of in situ transglutaminase 1 activity.Results: All patients presented with generalized ichthyosis, palmoplantar keratoderma, normal hair shafts, and significant oral manifestations. Natural evolution was relatively stable in all cases, without phenotype changing. Medical treatment with retinoids in patients 1 and 2 resulted in normalisation of the skin condition.Histological samples showed hyperkeratosis, acanthosisand perivascular inflammatory infiltrates in the dermis. Positive findings of transglutaminase 1 in situ activity excluded TGM1 deficiency. Direct sequencing of amplicons revealed one homozygous mutation in exon 4, a c.527C>A missense mutation.Conclusions: This is the first report of the hotspot mutation NIPAL4 c.527C>A in Romanian autosomal recessive congenital ichthyosis patients. The phenotype was similar to that reported in the literature, while transglutaminase 1 activity in situ assay detected differences in enzyme distribution between patients bearing the same mutation but different phenotypes. Based on the current data, NIPAL4 mutations are more frequent than TGM1 mutations in Romanian patients with autosomal recessive congenital ichthyosis.

NIPAL4 mutation c.527C˃A identified in Romanian patients with autosomal recessive congenital ichthyosis

Dermatology Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca,

Department of Cell and Molecular Biology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca,

Department of Cellular and Molecular Biology, University of Medicine and Pharmacy Tîrgu Mures,

Revista Romana de Medicina de Laborator

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Introduction: Autosomal recessive congenital ichthyosis is a non-syndromic ichthyosis, with a genetic background of mutations in 9 genes. This case series...

NIPAL4 mutation c.527C˃A identified in Romanian patients with autosomal recessive congenital ichthyosis

Published Online: Dec 30, 2016

Page range: 387 - 398

Received: Jun 07, 2016

Accepted: Sep 21, 2016

DOI: https://doi.org/10.1515/rrlm-2016-0034

Keywords
autosomal recessive congenital ichthyosis, NIPAL4 mutation, transglutaminase 1, electron microscopy

© 2016 Dalila Maier et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

NIPAL4 mutation c.527C˃A identified in Romanian patients with autosomal recessive congenital ichthyosis

Published Online: Dec 30, 2016

Page range: 387 - 398

Received: Jun 07, 2016

Accepted: Sep 21, 2016

DOI: https://doi.org/10.1515/rrlm-2016-0034

Keywordsautosomal recessive congenital ichthyosis, NIPAL4 mutation, transglutaminase 1, electron microscopy

© 2016 Dalila Maier et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
autosomal recessive congenital ichthyosis, NIPAL4 mutation, transglutaminase 1, electron microscopy