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Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations
Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identif...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303733/ https://www.ncbi.nlm.nih.gov/pubmed/34356170 http://dx.doi.org/10.3390/brainsci11070936 |
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author | Valentino, Floriana Bruno, Lucia Pia Doddato, Gabriella Giliberti, Annarita Tita, Rossella Resciniti, Sara Fallerini, Chiara Bruttini, Mirella Lo Rizzo, Caterina Mencarelli, Maria Antonietta Mari, Francesca Pinto, Anna Maria Fava, Francesca Baldassarri, Margherita Fabbiani, Alessandra Lamacchia, Vittoria Benetti, Elisa Zguro, Kristina Furini, Simone Renieri, Alessandra Ariani, Francesca |
author_facet | Valentino, Floriana Bruno, Lucia Pia Doddato, Gabriella Giliberti, Annarita Tita, Rossella Resciniti, Sara Fallerini, Chiara Bruttini, Mirella Lo Rizzo, Caterina Mencarelli, Maria Antonietta Mari, Francesca Pinto, Anna Maria Fava, Francesca Baldassarri, Margherita Fabbiani, Alessandra Lamacchia, Vittoria Benetti, Elisa Zguro, Kristina Furini, Simone Renieri, Alessandra Ariani, Francesca |
author_sort | Valentino, Floriana |
collection | PubMed |
description | Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that “reverse phenotyping” is fundamental to enlarge the phenotypic spectra associated with specific genes. |
format | Online Article Text |
id | pubmed-8303733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83037332021-07-25 Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations Valentino, Floriana Bruno, Lucia Pia Doddato, Gabriella Giliberti, Annarita Tita, Rossella Resciniti, Sara Fallerini, Chiara Bruttini, Mirella Lo Rizzo, Caterina Mencarelli, Maria Antonietta Mari, Francesca Pinto, Anna Maria Fava, Francesca Baldassarri, Margherita Fabbiani, Alessandra Lamacchia, Vittoria Benetti, Elisa Zguro, Kristina Furini, Simone Renieri, Alessandra Ariani, Francesca Brain Sci Article Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that “reverse phenotyping” is fundamental to enlarge the phenotypic spectra associated with specific genes. MDPI 2021-07-16 /pmc/articles/PMC8303733/ /pubmed/34356170 http://dx.doi.org/10.3390/brainsci11070936 Text en © 2021 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 Valentino, Floriana Bruno, Lucia Pia Doddato, Gabriella Giliberti, Annarita Tita, Rossella Resciniti, Sara Fallerini, Chiara Bruttini, Mirella Lo Rizzo, Caterina Mencarelli, Maria Antonietta Mari, Francesca Pinto, Anna Maria Fava, Francesca Baldassarri, Margherita Fabbiani, Alessandra Lamacchia, Vittoria Benetti, Elisa Zguro, Kristina Furini, Simone Renieri, Alessandra Ariani, Francesca Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations |
title | Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations |
title_full | Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations |
title_fullStr | Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations |
title_full_unstemmed | Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations |
title_short | Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations |
title_sort | exome sequencing in 200 intellectual disability/autistic patients: new candidates and atypical presentations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303733/ https://www.ncbi.nlm.nih.gov/pubmed/34356170 http://dx.doi.org/10.3390/brainsci11070936 |
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