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A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy

Complex genomic rearrangements (CGRs) are structural variants arising from two or more chromosomal breaks, which are challenging to characterize by conventional or molecular cytogenetic analysis (karyotype and FISH). The integrated approach of standard and genomic techniques, including optical genom...

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Autores principales: Orlando, Valeria, Di Tommaso, Silvia, Alesi, Viola, Loddo, Sara, Genovese, Silvia, Catino, Giorgia, Martucci, Licia, Roberti, Maria Cristina, Trivisano, Marina, Dentici, Maria Lisa, Specchio, Nicola, Dallapiccola, Bruno, Ferretti, Alessandro, Novelli, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656590/
https://www.ncbi.nlm.nih.gov/pubmed/36361691
http://dx.doi.org/10.3390/ijms232112900
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author Orlando, Valeria
Di Tommaso, Silvia
Alesi, Viola
Loddo, Sara
Genovese, Silvia
Catino, Giorgia
Martucci, Licia
Roberti, Maria Cristina
Trivisano, Marina
Dentici, Maria Lisa
Specchio, Nicola
Dallapiccola, Bruno
Ferretti, Alessandro
Novelli, Antonio
author_facet Orlando, Valeria
Di Tommaso, Silvia
Alesi, Viola
Loddo, Sara
Genovese, Silvia
Catino, Giorgia
Martucci, Licia
Roberti, Maria Cristina
Trivisano, Marina
Dentici, Maria Lisa
Specchio, Nicola
Dallapiccola, Bruno
Ferretti, Alessandro
Novelli, Antonio
author_sort Orlando, Valeria
collection PubMed
description Complex genomic rearrangements (CGRs) are structural variants arising from two or more chromosomal breaks, which are challenging to characterize by conventional or molecular cytogenetic analysis (karyotype and FISH). The integrated approach of standard and genomic techniques, including optical genome mapping (OGM) and genome sequencing, is crucial for disclosing and characterizing cryptic chromosomal rearrangements at high resolutions. We report on a patient with a complex developmental and epileptic encephalopathy in which karyotype analysis showed a de novo balanced translocation involving the long arms of chromosomes 2 and 18. Microarray analysis detected a 194 Kb microdeletion at 2q24.3 involving the SCN2A gene, which was considered the likely translocation breakpoint on chromosome 2. However, OGM redefined the translocation breakpoints by disclosing a paracentric inversion at 2q24.3 disrupting SCN1A. This combined genomic high-resolution approach allowed a fine characterization of the CGR, which involves two different chromosomes with four breakpoints. The patient’s phenotype resulted from the concomitant loss of function of SCN1A and SCN2A.
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spelling pubmed-96565902022-11-15 A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy Orlando, Valeria Di Tommaso, Silvia Alesi, Viola Loddo, Sara Genovese, Silvia Catino, Giorgia Martucci, Licia Roberti, Maria Cristina Trivisano, Marina Dentici, Maria Lisa Specchio, Nicola Dallapiccola, Bruno Ferretti, Alessandro Novelli, Antonio Int J Mol Sci Case Report Complex genomic rearrangements (CGRs) are structural variants arising from two or more chromosomal breaks, which are challenging to characterize by conventional or molecular cytogenetic analysis (karyotype and FISH). The integrated approach of standard and genomic techniques, including optical genome mapping (OGM) and genome sequencing, is crucial for disclosing and characterizing cryptic chromosomal rearrangements at high resolutions. We report on a patient with a complex developmental and epileptic encephalopathy in which karyotype analysis showed a de novo balanced translocation involving the long arms of chromosomes 2 and 18. Microarray analysis detected a 194 Kb microdeletion at 2q24.3 involving the SCN2A gene, which was considered the likely translocation breakpoint on chromosome 2. However, OGM redefined the translocation breakpoints by disclosing a paracentric inversion at 2q24.3 disrupting SCN1A. This combined genomic high-resolution approach allowed a fine characterization of the CGR, which involves two different chromosomes with four breakpoints. The patient’s phenotype resulted from the concomitant loss of function of SCN1A and SCN2A. MDPI 2022-10-26 /pmc/articles/PMC9656590/ /pubmed/36361691 http://dx.doi.org/10.3390/ijms232112900 Text en © 2022 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 Case Report
Orlando, Valeria
Di Tommaso, Silvia
Alesi, Viola
Loddo, Sara
Genovese, Silvia
Catino, Giorgia
Martucci, Licia
Roberti, Maria Cristina
Trivisano, Marina
Dentici, Maria Lisa
Specchio, Nicola
Dallapiccola, Bruno
Ferretti, Alessandro
Novelli, Antonio
A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
title A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
title_full A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
title_fullStr A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
title_full_unstemmed A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
title_short A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
title_sort complex genomic rearrangement resulting in loss of function of scn1a and scn2a in a patient with severe developmental and epileptic encephalopathy
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656590/
https://www.ncbi.nlm.nih.gov/pubmed/36361691
http://dx.doi.org/10.3390/ijms232112900
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