Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder

Introduction: Clinical genomics promise to be especially suitable for the study of etiologically heterogeneous conditions such as Autism Spectrum Disorder (ASD). Here we present three siblings with ASD where we evaluated the usefulness of Whole Genome Sequencing (WGS) for the diagnostic approach to...

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Autores principales:	Nemirovsky, Sergio I., Ogara, Maria Florencia, Pecci, Adali, Martí, Marcelo Adrián, Vazquez, Martín Pablo, Turjanski, Adrián Gustavo
Publicado:	2015
Materias:	cytosine nerve protein SHANK3 protein, human Article autism bioinformatics case report clinical feature codon disease severity epilepsy exon family history family study gene deletion gene location gene mutation gene sequence genetic variability germ line heterozygosity human intellectual impairment language disability male mental deficiency mental disease missense mutation mosaicism parent Sanger sequencing sequence analysis SHANK3 gene sibling stop codon Whole Genome Sequencing child dna mutational analysis female genetics genomics mutation nucleotide sequence pedigree preschool child Autism Spectrum Disorder Base Sequence Child Child, Preschool DNA Mutational Analysis Female Genomics Humans Male Mosaicism Mutation Nerve Tissue Proteins Pedigree Siblings
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n2_p_Nemirovsky http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Nemirovsky
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_19326203_v10_n2_p_Nemirovsky
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spelling	paper:paper_19326203_v10_n2_p_Nemirovsky2023-06-08T16:30:28Z Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder Nemirovsky, Sergio I. Ogara, Maria Florencia Pecci, Adali Martí, Marcelo Adrián Vazquez, Martín Pablo Turjanski, Adrián Gustavo cytosine nerve protein SHANK3 protein, human Article autism bioinformatics case report clinical feature codon disease severity epilepsy exon family history family study gene deletion gene location gene mutation gene sequence genetic variability germ line heterozygosity human intellectual impairment language disability male mental deficiency mental disease missense mutation mosaicism parent Sanger sequencing sequence analysis SHANK3 gene sibling stop codon Whole Genome Sequencing autism child dna mutational analysis female genetics genomics mutation nucleotide sequence pedigree preschool child Autism Spectrum Disorder Base Sequence Child Child, Preschool DNA Mutational Analysis Female Genomics Humans Male Mosaicism Mutation Nerve Tissue Proteins Pedigree Siblings Introduction: Clinical genomics promise to be especially suitable for the study of etiologically heterogeneous conditions such as Autism Spectrum Disorder (ASD). Here we present three siblings with ASD where we evaluated the usefulness of Whole Genome Sequencing (WGS) for the diagnostic approach to ASD. Methods: We identified a family segregating ASD in three siblings with an unidentified cause. We performed WGS in the three probands and used a state-of-the-art comprehensive bioinformatic analysis pipeline and prioritized the identified variants located in genes likely to be related to ASD. We validated the finding by Sanger sequencing in the probands and their parents. Results: Three male siblings presented a syndrome characterized by severe intellectual disability, absence of language, autism spectrum symptoms and epilepsy with negative family history for mental retardation, language disorders, ASD or other psychiatric disorders. We found germline mosaicism for a heterozygous deletion of a cytosine in the exon 21 of the SHANK3 gene, resulting in a missense sequence of 5 codons followed by a premature stop codon (NM-033517:c.3259-3259delC, p.Ser1088Profs∗6). Conclusions: We reported an infrequent form of familial ASD where WGS proved useful in the clinic. We identified a mutation in SHANK3 that underscores its relevance in Autism Spectrum Disorder. © 2015 Nemirovsky et al. Fil:Nemirovsky, S.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ogara, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pecci, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vazquez, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Turjanski, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n2_p_Nemirovsky http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Nemirovsky
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	cytosine nerve protein SHANK3 protein, human Article autism bioinformatics case report clinical feature codon disease severity epilepsy exon family history family study gene deletion gene location gene mutation gene sequence genetic variability germ line heterozygosity human intellectual impairment language disability male mental deficiency mental disease missense mutation mosaicism parent Sanger sequencing sequence analysis SHANK3 gene sibling stop codon Whole Genome Sequencing autism child dna mutational analysis female genetics genomics mutation nucleotide sequence pedigree preschool child Autism Spectrum Disorder Base Sequence Child Child, Preschool DNA Mutational Analysis Female Genomics Humans Male Mosaicism Mutation Nerve Tissue Proteins Pedigree Siblings
spellingShingle	cytosine nerve protein SHANK3 protein, human Article autism bioinformatics case report clinical feature codon disease severity epilepsy exon family history family study gene deletion gene location gene mutation gene sequence genetic variability germ line heterozygosity human intellectual impairment language disability male mental deficiency mental disease missense mutation mosaicism parent Sanger sequencing sequence analysis SHANK3 gene sibling stop codon Whole Genome Sequencing autism child dna mutational analysis female genetics genomics mutation nucleotide sequence pedigree preschool child Autism Spectrum Disorder Base Sequence Child Child, Preschool DNA Mutational Analysis Female Genomics Humans Male Mosaicism Mutation Nerve Tissue Proteins Pedigree Siblings Nemirovsky, Sergio I. Ogara, Maria Florencia Pecci, Adali Martí, Marcelo Adrián Vazquez, Martín Pablo Turjanski, Adrián Gustavo Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
topic_facet	cytosine nerve protein SHANK3 protein, human Article autism bioinformatics case report clinical feature codon disease severity epilepsy exon family history family study gene deletion gene location gene mutation gene sequence genetic variability germ line heterozygosity human intellectual impairment language disability male mental deficiency mental disease missense mutation mosaicism parent Sanger sequencing sequence analysis SHANK3 gene sibling stop codon Whole Genome Sequencing autism child dna mutational analysis female genetics genomics mutation nucleotide sequence pedigree preschool child Autism Spectrum Disorder Base Sequence Child Child, Preschool DNA Mutational Analysis Female Genomics Humans Male Mosaicism Mutation Nerve Tissue Proteins Pedigree Siblings
description	Introduction: Clinical genomics promise to be especially suitable for the study of etiologically heterogeneous conditions such as Autism Spectrum Disorder (ASD). Here we present three siblings with ASD where we evaluated the usefulness of Whole Genome Sequencing (WGS) for the diagnostic approach to ASD. Methods: We identified a family segregating ASD in three siblings with an unidentified cause. We performed WGS in the three probands and used a state-of-the-art comprehensive bioinformatic analysis pipeline and prioritized the identified variants located in genes likely to be related to ASD. We validated the finding by Sanger sequencing in the probands and their parents. Results: Three male siblings presented a syndrome characterized by severe intellectual disability, absence of language, autism spectrum symptoms and epilepsy with negative family history for mental retardation, language disorders, ASD or other psychiatric disorders. We found germline mosaicism for a heterozygous deletion of a cytosine in the exon 21 of the SHANK3 gene, resulting in a missense sequence of 5 codons followed by a premature stop codon (NM-033517:c.3259-3259delC, p.Ser1088Profs∗6). Conclusions: We reported an infrequent form of familial ASD where WGS proved useful in the clinic. We identified a mutation in SHANK3 that underscores its relevance in Autism Spectrum Disorder. © 2015 Nemirovsky et al.
author	Nemirovsky, Sergio I. Ogara, Maria Florencia Pecci, Adali Martí, Marcelo Adrián Vazquez, Martín Pablo Turjanski, Adrián Gustavo
author_facet	Nemirovsky, Sergio I. Ogara, Maria Florencia Pecci, Adali Martí, Marcelo Adrián Vazquez, Martín Pablo Turjanski, Adrián Gustavo
author_sort	Nemirovsky, Sergio I.
title	Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
title_short	Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
title_full	Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
title_fullStr	Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
title_full_unstemmed	Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
title_sort	whole genome sequencing reveals a de novo shank3 mutation in familial autism spectrum disorder
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n2_p_Nemirovsky http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Nemirovsky
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Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder

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