Cargando…

Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients

Autosomal recessive congenital ichthyoses (ARCI) are rare genodermatosis disorders characterized by phenotypic and genetic heterogeneity. At least fourteen genes so far have been related to ARCI; however, despite genetic heterogeneity, phenotypes associated with mutation of different ARCI genes may...

Descripción completa

Detalles Bibliográficos
Autores principales: Fioretti, Tiziana, Auricchio, Luigi, Piccirillo, Angelo, Vitiello, Giuseppina, Ambrosio, Adelaide, Cattaneo, Fabio, Ammendola, Rosario, Esposito, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760754/
https://www.ncbi.nlm.nih.gov/pubmed/33255364
http://dx.doi.org/10.3390/diagnostics10120995
_version_ 1783627408042098688
author Fioretti, Tiziana
Auricchio, Luigi
Piccirillo, Angelo
Vitiello, Giuseppina
Ambrosio, Adelaide
Cattaneo, Fabio
Ammendola, Rosario
Esposito, Gabriella
author_facet Fioretti, Tiziana
Auricchio, Luigi
Piccirillo, Angelo
Vitiello, Giuseppina
Ambrosio, Adelaide
Cattaneo, Fabio
Ammendola, Rosario
Esposito, Gabriella
author_sort Fioretti, Tiziana
collection PubMed
description Autosomal recessive congenital ichthyoses (ARCI) are rare genodermatosis disorders characterized by phenotypic and genetic heterogeneity. At least fourteen genes so far have been related to ARCI; however, despite genetic heterogeneity, phenotypes associated with mutation of different ARCI genes may overlap, thereby making difficult their clinical and molecular classification. In addition, molecular tests for diagnosis of such an extremely rare heterogeneous inherited disease are not easily available in clinical settings. In the attempt of identifying the genetic cause of the disease in four Italian patients with ARCI, we performed next-generation sequencing (NGS) analysis targeting 4811 genes that have been previously linked to human genetic diseases; we focused our analysis on the 13 known ARCI genes comprised in the panel. Nine different variants including three novel small nucleotide changes and two novel large deletions have been identified and validated in the ABCA12, ALOX12B, CYP4F22, and SULT2B1 genes. Notably, two patients had variants in more than one gene. The identification and validation of new pathogenic ABCA12, ALOX12B, CYP4F22, and SULT2B1 variants through multi-gene NGS in four cases of ARCI further highlight the importance of these genes in proper skin function and development.
format Online
Article
Text
id pubmed-7760754
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77607542020-12-26 Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients Fioretti, Tiziana Auricchio, Luigi Piccirillo, Angelo Vitiello, Giuseppina Ambrosio, Adelaide Cattaneo, Fabio Ammendola, Rosario Esposito, Gabriella Diagnostics (Basel) Article Autosomal recessive congenital ichthyoses (ARCI) are rare genodermatosis disorders characterized by phenotypic and genetic heterogeneity. At least fourteen genes so far have been related to ARCI; however, despite genetic heterogeneity, phenotypes associated with mutation of different ARCI genes may overlap, thereby making difficult their clinical and molecular classification. In addition, molecular tests for diagnosis of such an extremely rare heterogeneous inherited disease are not easily available in clinical settings. In the attempt of identifying the genetic cause of the disease in four Italian patients with ARCI, we performed next-generation sequencing (NGS) analysis targeting 4811 genes that have been previously linked to human genetic diseases; we focused our analysis on the 13 known ARCI genes comprised in the panel. Nine different variants including three novel small nucleotide changes and two novel large deletions have been identified and validated in the ABCA12, ALOX12B, CYP4F22, and SULT2B1 genes. Notably, two patients had variants in more than one gene. The identification and validation of new pathogenic ABCA12, ALOX12B, CYP4F22, and SULT2B1 variants through multi-gene NGS in four cases of ARCI further highlight the importance of these genes in proper skin function and development. MDPI 2020-11-24 /pmc/articles/PMC7760754/ /pubmed/33255364 http://dx.doi.org/10.3390/diagnostics10120995 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fioretti, Tiziana
Auricchio, Luigi
Piccirillo, Angelo
Vitiello, Giuseppina
Ambrosio, Adelaide
Cattaneo, Fabio
Ammendola, Rosario
Esposito, Gabriella
Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients
title Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients
title_full Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients
title_fullStr Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients
title_full_unstemmed Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients
title_short Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients
title_sort multi-gene next-generation sequencing for molecular diagnosis of autosomal recessive congenital ichthyosis: a genotype-phenotype study of four italian patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760754/
https://www.ncbi.nlm.nih.gov/pubmed/33255364
http://dx.doi.org/10.3390/diagnostics10120995
work_keys_str_mv AT fiorettitiziana multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT auricchioluigi multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT piccirilloangelo multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT vitiellogiuseppina multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT ambrosioadelaide multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT cattaneofabio multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT ammendolarosario multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients
AT espositogabriella multigenenextgenerationsequencingformoleculardiagnosisofautosomalrecessivecongenitalichthyosisagenotypephenotypestudyoffouritalianpatients