Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder.
<h4>Introduction</h4>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 diag...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0116358&type=printable |
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| author | Sergio I Nemirovsky Marta Córdoba Jonathan J Zaiat Sabrina P Completa Patricia A Vega Dolores González-Morón Nancy M Medina Mónica Fabbro Soledad Romero Bianca Brun Santiago Revale María Florencia Ogara Adali Pecci Marcelo Marti Martin Vazquez Adrián Turjanski Marcelo A Kauffman |
| author_facet | Sergio I Nemirovsky Marta Córdoba Jonathan J Zaiat Sabrina P Completa Patricia A Vega Dolores González-Morón Nancy M Medina Mónica Fabbro Soledad Romero Bianca Brun Santiago Revale María Florencia Ogara Adali Pecci Marcelo Marti Martin Vazquez Adrián Turjanski Marcelo A Kauffman |
| author_sort | Sergio I Nemirovsky |
| collection | DOAJ |
| description | <h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-2a5d28e82d2f4c298924f9305dbc1fc3 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2a5d28e82d2f4c298924f9305dbc1fc32025-08-20T02:15:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011635810.1371/journal.pone.0116358Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder.Sergio I NemirovskyMarta CórdobaJonathan J ZaiatSabrina P CompletaPatricia A VegaDolores González-MorónNancy M MedinaMónica FabbroSoledad RomeroBianca BrunSantiago RevaleMaría Florencia OgaraAdali PecciMarcelo MartiMartin VazquezAdrián TurjanskiMarcelo A Kauffman<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0116358&type=printable |
| spellingShingle | Sergio I Nemirovsky Marta Córdoba Jonathan J Zaiat Sabrina P Completa Patricia A Vega Dolores González-Morón Nancy M Medina Mónica Fabbro Soledad Romero Bianca Brun Santiago Revale María Florencia Ogara Adali Pecci Marcelo Marti Martin Vazquez Adrián Turjanski Marcelo A Kauffman Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder. PLoS ONE |
| title | 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_short | 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 | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0116358&type=printable |
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