Cargando…

Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results

ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The stu...

Descripción completa

Detalles Bibliográficos
Autores principales: Lintas, Carla, Sacco, Roberto, Azzarà, Alessia, Cassano, Ilaria, Gurrieri, Fiorella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584959/
https://www.ncbi.nlm.nih.gov/pubmed/34768579
http://dx.doi.org/10.3390/jcm10215060
_version_ 1784597574601146368
author Lintas, Carla
Sacco, Roberto
Azzarà, Alessia
Cassano, Ilaria
Gurrieri, Fiorella
author_facet Lintas, Carla
Sacco, Roberto
Azzarà, Alessia
Cassano, Ilaria
Gurrieri, Fiorella
author_sort Lintas, Carla
collection PubMed
description ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The study identified 102 genes which are de novo mutated in subjects affected by autism spectrum disorder (ASD) or similar neurodevelopmental disorders (NDDs). The majority of these genes was already known to be implicated in ASD or NDDs, whereas approximately 30 genes were considered “novel” as either they were not previously associated with ASD/NDDs or very little information about them was present in the literature. The aim of this work is to review the current literature since the publication of the ASC paper to see if new data mainly concerning genotype–phenotype correlations of the novel genes have been added to the existing one. We found new important clinical and molecular data for 6 of the 30 novel genes. Though the broad and overlapping neurodevelopmental phenotypes observed in most monogenic forms of NDDs make it difficult for the clinical geneticist to address gene-specific tests, knowledge of these new data can at least help to prioritize and interpret results of pangenomic tests to some extent. Indeed, for some of the new emerging genes analyzed in the present work, specific clinical features emerged that may help the clinical geneticist to make the final diagnosis by associating the genetic test results with the phenotype. The importance of this relatively new approach known as “reverse phenotyping” will be discussed.
format Online
Article
Text
id pubmed-8584959
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85849592021-11-12 Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results Lintas, Carla Sacco, Roberto Azzarà, Alessia Cassano, Ilaria Gurrieri, Fiorella J Clin Med Review ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The study identified 102 genes which are de novo mutated in subjects affected by autism spectrum disorder (ASD) or similar neurodevelopmental disorders (NDDs). The majority of these genes was already known to be implicated in ASD or NDDs, whereas approximately 30 genes were considered “novel” as either they were not previously associated with ASD/NDDs or very little information about them was present in the literature. The aim of this work is to review the current literature since the publication of the ASC paper to see if new data mainly concerning genotype–phenotype correlations of the novel genes have been added to the existing one. We found new important clinical and molecular data for 6 of the 30 novel genes. Though the broad and overlapping neurodevelopmental phenotypes observed in most monogenic forms of NDDs make it difficult for the clinical geneticist to address gene-specific tests, knowledge of these new data can at least help to prioritize and interpret results of pangenomic tests to some extent. Indeed, for some of the new emerging genes analyzed in the present work, specific clinical features emerged that may help the clinical geneticist to make the final diagnosis by associating the genetic test results with the phenotype. The importance of this relatively new approach known as “reverse phenotyping” will be discussed. MDPI 2021-10-29 /pmc/articles/PMC8584959/ /pubmed/34768579 http://dx.doi.org/10.3390/jcm10215060 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 Review
Lintas, Carla
Sacco, Roberto
Azzarà, Alessia
Cassano, Ilaria
Gurrieri, Fiorella
Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results
title Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results
title_full Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results
title_fullStr Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results
title_full_unstemmed Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results
title_short Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results
title_sort genotype–phenotype correlations in relation to newly emerging monogenic forms of autism spectrum disorder and associated neurodevelopmental disorders: the importance of phenotype reevaluation after pangenomic results
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584959/
https://www.ncbi.nlm.nih.gov/pubmed/34768579
http://dx.doi.org/10.3390/jcm10215060
work_keys_str_mv AT lintascarla genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults
AT saccoroberto genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults
AT azzaraalessia genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults
AT cassanoilaria genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults
AT gurrierifiorella genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults