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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" (2015) PLoS ONE. 10(2)
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Abstract:

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.

Registro:

Documento: Artículo
Título:Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder
Autor: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.
Filiación:Plataforma de Bioinformática Argentina, Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, UBA, Pabellón 2, Ciudad Universitaria, Buenos Aires, Argentina
Instituto de Agrobiotecnología de Rosario (INDEAR), CONICET, Predio CCT, Rosario, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, INQUIMAE/CONICET, Pabellón 2, Ciudad Universitaria, Buenos Aires, Argentina
Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejía, IBCN Eduardo de Robertis UBA-CONICET, Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave: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
Año:2015
Volumen:10
Número:2
DOI: http://dx.doi.org/10.1371/journal.pone.0116358
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:cytosine, 71-30-7; Nerve Tissue Proteins; SHANK3 protein, human
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n2_p_Nemirovsky

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Citas:

---------- APA ----------
Nemirovsky, S.I., Córdoba, M., Zaiat, J.J., Completa, S.P., Vega, P.A., González-Morón, D., Medina, N.M.,..., Kauffman, M.A. (2015) . Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder. PLoS ONE, 10(2).
http://dx.doi.org/10.1371/journal.pone.0116358
---------- CHICAGO ----------
Nemirovsky, S.I., Córdoba, M., Zaiat, J.J., Completa, S.P., Vega, P.A., González-Morón, D., et al. "Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder" . PLoS ONE 10, no. 2 (2015).
http://dx.doi.org/10.1371/journal.pone.0116358
---------- MLA ----------
Nemirovsky, S.I., Córdoba, M., Zaiat, J.J., Completa, S.P., Vega, P.A., González-Morón, D., et al. "Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder" . PLoS ONE, vol. 10, no. 2, 2015.
http://dx.doi.org/10.1371/journal.pone.0116358
---------- VANCOUVER ----------
Nemirovsky, S.I., Córdoba, M., Zaiat, J.J., Completa, S.P., Vega, P.A., González-Morón, D., et al. Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder. PLoS ONE. 2015;10(2).
http://dx.doi.org/10.1371/journal.pone.0116358