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Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mut...

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Autores principales: Hotz, Alrun, Kopp, Julia, Bourrat, Emmanuelle, Oji, Vinzenz, Süßmuth, Kira, Komlosi, Katalin, Bouadjar, Bakar, Tantcheva-Poór, Iliana, Hellström Pigg, Maritta, Betz, Regina C., Giehl, Kathrin, Schedel, Fiona, Weibel, Lisa, Schulz, Solveig, Stölzl, Dora V., Tadini, Gianluca, Demiral, Emine, Berggard, Karin, Zimmer, Andreas D., Alter, Svenja, Fischer, Judith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048568/
https://www.ncbi.nlm.nih.gov/pubmed/36980989
http://dx.doi.org/10.3390/genes14030717
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author Hotz, Alrun
Kopp, Julia
Bourrat, Emmanuelle
Oji, Vinzenz
Süßmuth, Kira
Komlosi, Katalin
Bouadjar, Bakar
Tantcheva-Poór, Iliana
Hellström Pigg, Maritta
Betz, Regina C.
Giehl, Kathrin
Schedel, Fiona
Weibel, Lisa
Schulz, Solveig
Stölzl, Dora V.
Tadini, Gianluca
Demiral, Emine
Berggard, Karin
Zimmer, Andreas D.
Alter, Svenja
Fischer, Judith
author_facet Hotz, Alrun
Kopp, Julia
Bourrat, Emmanuelle
Oji, Vinzenz
Süßmuth, Kira
Komlosi, Katalin
Bouadjar, Bakar
Tantcheva-Poór, Iliana
Hellström Pigg, Maritta
Betz, Regina C.
Giehl, Kathrin
Schedel, Fiona
Weibel, Lisa
Schulz, Solveig
Stölzl, Dora V.
Tadini, Gianluca
Demiral, Emine
Berggard, Karin
Zimmer, Andreas D.
Alter, Svenja
Fischer, Judith
author_sort Hotz, Alrun
collection PubMed
description Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI.
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spelling pubmed-100485682023-03-29 Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis Hotz, Alrun Kopp, Julia Bourrat, Emmanuelle Oji, Vinzenz Süßmuth, Kira Komlosi, Katalin Bouadjar, Bakar Tantcheva-Poór, Iliana Hellström Pigg, Maritta Betz, Regina C. Giehl, Kathrin Schedel, Fiona Weibel, Lisa Schulz, Solveig Stölzl, Dora V. Tadini, Gianluca Demiral, Emine Berggard, Karin Zimmer, Andreas D. Alter, Svenja Fischer, Judith Genes (Basel) Article Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI. MDPI 2023-03-15 /pmc/articles/PMC10048568/ /pubmed/36980989 http://dx.doi.org/10.3390/genes14030717 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hotz, Alrun
Kopp, Julia
Bourrat, Emmanuelle
Oji, Vinzenz
Süßmuth, Kira
Komlosi, Katalin
Bouadjar, Bakar
Tantcheva-Poór, Iliana
Hellström Pigg, Maritta
Betz, Regina C.
Giehl, Kathrin
Schedel, Fiona
Weibel, Lisa
Schulz, Solveig
Stölzl, Dora V.
Tadini, Gianluca
Demiral, Emine
Berggard, Karin
Zimmer, Andreas D.
Alter, Svenja
Fischer, Judith
Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
title Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
title_full Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
title_fullStr Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
title_full_unstemmed Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
title_short Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
title_sort mutational spectrum of the abca12 gene and genotype–phenotype correlation in a cohort of 64 patients with autosomal recessive congenital ichthyosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048568/
https://www.ncbi.nlm.nih.gov/pubmed/36980989
http://dx.doi.org/10.3390/genes14030717
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