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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todo:paper_19326203_v10_n2_p_Nemirovsky2023-10-03T16:34:35Z Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder Nemirovsky, S.I. Córdoba, M. Zaiat, J.J. Completa, S.P. Vega, P.A. González-Morón, D. Medina, N.M. Fabbro, M. Romero, S. Brun, B. Revale, S. Ogara, M.F. Pecci, A. Marti, M. Vazquez, M. Turjanski, A. Kauffman, M.A. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Nemirovsky |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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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, S.I. Córdoba, M. Zaiat, J.J. Completa, S.P. Vega, P.A. González-Morón, D. Medina, N.M. Fabbro, M. Romero, S. Brun, B. Revale, S. Ogara, M.F. Pecci, A. Marti, M. Vazquez, M. Turjanski, A. Kauffman, M.A. 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. |
| format |
JOUR |
| author |
Nemirovsky, S.I. Córdoba, M. Zaiat, J.J. Completa, S.P. Vega, P.A. González-Morón, D. Medina, N.M. Fabbro, M. Romero, S. Brun, B. Revale, S. Ogara, M.F. Pecci, A. Marti, M. Vazquez, M. Turjanski, A. Kauffman, M.A. |
| author_facet |
Nemirovsky, S.I. Córdoba, M. Zaiat, J.J. Completa, S.P. Vega, P.A. González-Morón, D. Medina, N.M. Fabbro, M. Romero, S. Brun, B. Revale, S. Ogara, M.F. Pecci, A. Marti, M. Vazquez, M. Turjanski, A. Kauffman, M.A. |
| author_sort |
Nemirovsky, S.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 |
| url |
http://hdl.handle.net/20.500.12110/paper_19326203_v10_n2_p_Nemirovsky |
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