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

Guardado en:

Detalles Bibliográficos
Autores principales:	Carla Lintas, Roberto Sacco, Alessia Azzarà, Ilaria Cassano, Fiorella Gurrieri
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autism spectrum disorder neurodevelopmental disorders exome sequencing phenotype reevaluation ASD NDDs Medicine R
Acceso en línea:	https://doaj.org/article/e642b7f64a9942068e25747356164834
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e642b7f64a9942068e25747356164834
record_format	dspace
spelling	oai:doaj.org-article:e642b7f64a9942068e257473561648342021-11-11T17:41:03ZGenotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results10.3390/jcm102150602077-0383https://doaj.org/article/e642b7f64a9942068e257473561648342021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/5060https://doaj.org/toc/2077-0383ASD 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.Carla LintasRoberto SaccoAlessia AzzaràIlaria CassanoFiorella GurrieriMDPI AGarticleautism spectrum disorderneurodevelopmental disordersexome sequencingphenotype reevaluationASDNDDsMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5060, p 5060 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism spectrum disorder neurodevelopmental disorders exome sequencing phenotype reevaluation ASD NDDs Medicine R
spellingShingle	autism spectrum disorder neurodevelopmental disorders exome sequencing phenotype reevaluation ASD NDDs Medicine R Carla Lintas Roberto Sacco Alessia Azzarà Ilaria Cassano Fiorella Gurrieri 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
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	article
author	Carla Lintas Roberto Sacco Alessia Azzarà Ilaria Cassano Fiorella Gurrieri
author_facet	Carla Lintas Roberto Sacco Alessia Azzarà Ilaria Cassano Fiorella Gurrieri
author_sort	Carla Lintas
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_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_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_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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e642b7f64a9942068e25747356164834
work_keys_str_mv	AT carlalintas genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults AT robertosacco genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults AT alessiaazzara genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults AT ilariacassano genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults AT fiorellagurrieri genotypephenotypecorrelationsinrelationtonewlyemergingmonogenicformsofautismspectrumdisorderandassociatedneurodevelopmentaldisorderstheimportanceofphenotypereevaluationafterpangenomicresults
_version_	1718432032843890688

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

Ejemplares similares