A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in  NIPAL4/Ichthyin

Kusakabe, Minori; Nagai, Makoto; Nakano, Eiji; Jitsukawa, Orie; Nishigori, Chikako; Yamanishi, Kiyofumi

doi:10.2340/00015555-2550

Cited by 6 publications

(4 citation statements)

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“…Disrupted terminal differentiation, lipid homeostasis, increased TEWL, and associations with atopy have historically linked ichthyoses to AD. 2,3,18,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]43,[50][51][52][83][84][85][86] However, our recent profiling of ichthyotic skin using a limited geneexpression approach demonstrated enhanced T H 17/IL-23 response with marginal T H 2 skewing and lack of abnormalities in 3 differentiation proteins (FLG, LOR, and PPL), aligning it more closely to the psoriasis profile. 53 The present study is the first comprehensive genomic skin fingerprinting of the most common orphan ichthyosis subtypes to J ALLERGY CLIN IMMUNOL VOLUME 143, NUMBER 2 FIG 5.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20][21][22][23][24][25][26] Human skin and blood studies have been limited to a few patients or select ichthyosis subtypes and have shown abnormalities in lipid, cornified envelope (CE), and/or other differentiation measures. 18,[27][28][29][30][31][32][33][34][35][36][37][38][39][40] Several observations link ichthyoses, particularly Netherton syndrome (NS), to atopic dermatitis (AD), which is marked by epidermal barrier defects and immune dysregulation. 41 NS shares the eosinophilia and increased T H 2/atopy-related markers (thymic stromal lymphopoietin [TSLP], chemokine like 17 [CCL17]/ thymus and activation-regulated chemokine, and IgE) of AD, 18,20,[42][43][44][45][46][47][48][49] and polymorphisms of serine protease inhibitor, Kazal-type 5 (mutated in patients with NS) are associated with AD.…”

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confidence: 99%

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Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature

Malik

Huynh

et al. 2019

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature

Malik

Huynh

et al. 2019

Journal of Allergy and Clinical Immunology

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“…Nipa‐Like Domain‐Containing 4 ( NIPAL4 ) is the second most commonly mutated gene in ARCI after TGM1 (11–16% in NIPAL4 , Fischer, ; Vahlquist, Fischer, & Törmä, ) and is predicted to encode a transmembrane protein with nine transmembrane domains (Lefèvre et al, ). Since its first identification by Lefèvre et al, in 2004, 18 disease‐causing mutations have been reported in NIPAL4 including the highly recurrent mutation c.527C>A, p.(Ala176Asp; Balci et al, ; Bučková et al, ; Dahlqvist et al, ; Kusakabe et al, ; Lefèvre et al, ; Maier, Mazereeuw‐Hautier, Tilinca, Cosgarea, & Jonca, ; Palamar et al, ; Scott et al, ; Wajid, Kurban, Shimomura, & Christiano, ). Clinical phenotypes in this molecular genetically characterized subgroup of ARCI are heterogeneous and show interfamilial, intrafamilial, and intraindividual variability (Alavi et al, ; Vahlquist et al, ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 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. OneThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.*Nadja Ballin and Alrun Hotz contributed equally to this work. 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, a potential hot spot for mutations, and genotype-phenotype correlations. K E Y W O R D SARCI, ARCI EM type III, collodion baby, ichthyosis, NIPAL4

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“…In fact, the nine transmembrane helices form a basket‐shaped fold with a large substrate‐binding cavity at the center of the molecule. The Mutation p.E178D, located in the second transmembrane alpha helix, could therefore affect the transportation function of the protein, as described previously (Kusakabe et al, ). Previous studies hypothesized that NIPA4 protein is an Mg 2+ transporter protein based on the prediction of the secondary structure of the protein (Goytain et al, )(Mauldin et al, ).…”

Section: Discussionmentioning

confidence: 91%

Identification of a novel missense mutation in NIPAL4 gene: First 3D model construction predicted its pathogenicity

Laadhar¹,

Mansour²,

Marrakchi

et al. 2019

Molec Gen & Gen Med

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Background The NIPAL4 gene is described to be implicated of Congenital Ichthyosiform Erythroderma (CIE). It encodes a magnesium transporter membrane‐associated protein, hypothetically involved in epidermal lipid processing and in lamellar body formation. The aim of this work is to investigate the causative mutation in a consanguineous Tunisian family with a clinical feature of CIE with a yellowish severe palmoplantar keratoderma. Methods Four patients were dignosed with CIE. The blood samples were collected from patients and all members of their nuclear family for mutation analysis. The novel mutation of NIPAL4 gene was analysed with several software tools to predict its pathogenicity. Then, the secondary structure and the 3D model of ichthyn was generated in silico. Results The sequencing analysis of the NIPAL4 gene in patients revealed a novel homozygous missense mutation c.534A>C (p.E178D) in the exon 4. Bioinformatic tools predicted its pathogenicity. The secondary structure prediction and the 3D model construction expected the presence of 9 transmembrane helices and revealed that mutation p.E178D was located in the middle of the second transmembrane helices. Besides, the 3D model construction revealed that the p.E178D mutation is inducing a shrinking in the transport channel containing the mutated NIPA4 protein. Conclusion We found a homozygous mutation in exon 4 of NIPAL4 c.534A>C (p.E178D), which was identified for the first time in our study. Bioinformatic investigations supported its involvement in the phenotype of patients with CIE. Interestingly, this mutation was located in the hypothetical transport channel cavity and leads to changes in the channel architecture, which would probably affect its transport function.

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A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in NIPAL4/Ichthyin

Cited by 6 publications

References 5 publications

Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature

Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature

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

Identification of a novel missense mutation in NIPAL4 gene: First 3D model construction predicted its pathogenicity

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