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A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder.
Loureiro, Livia O; Howe, Jennifer L; Reuter, Miriam S; Iaboni, Alana; Calli, Kristina; Roshandel, Delnaz; Pritisanac, Iva; Moses, Alan; Forman-Kay, Julie D; Trost, Brett; Zarrei, Mehdi; Rennie, Olivia; Lau, Lynette Y S; Marshall, Christian R; Srivastava, Siddharth; Godlewski, Brianna; Buttermore, Elizabeth D; Sahin, Mustafa; Hartley, Dean; Frazier, Thomas; Vorstman, Jacob; Georgiades, Stelios; Lewis, Suzanne M E; Szatmari, Peter; Bradley, Clarrisa A Lisa; Tabet, Anne-Claude; Willems, Marjolaine; Lumbroso, Serge; Piton, Amélie; Lespinasse, James; Delorme, Richard; Bourgeron, Thomas; Anagnostou, Evdokia; Scherer, Stephen W.
Afiliación
  • Loureiro LO; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Howe JL; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Reuter MS; Canada's Genomics Enterprise (CGEn), The Hospital for Sick Children, Toronto, ON, Canada.
  • Iaboni A; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
  • Calli K; Department of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
  • Roshandel D; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Pritisanac I; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
  • Moses A; Department of Cell & Systems Biology, University of Toronto, Toronto, ON, Canada.
  • Forman-Kay JD; Department of Cell & Systems Biology, University of Toronto, Toronto, ON, Canada.
  • Trost B; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
  • Zarrei M; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
  • Rennie O; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Lau LYS; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Marshall CR; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Srivastava S; Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
  • Godlewski B; Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
  • Buttermore ED; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Sahin M; Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Hartley D; Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Frazier T; Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Vorstman J; Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Georgiades S; Autism Speaks, New York, NY, USA.
  • Lewis SME; Autism Speaks and Department of Psychology, John Carroll University, Cleveland, OH, USA.
  • Szatmari P; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
  • Bradley CAL; Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.
  • Tabet AC; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
  • Willems M; Department of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
  • Lumbroso S; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
  • Piton A; Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.
  • Lespinasse J; Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Delorme R; Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
  • Bourgeron T; Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, F-75015, Paris, France.
  • Anagnostou E; Genetics Department, Cytogenetic Unit, Robert Debré Hospital, APHP, F-75019, Paris, France.
  • Scherer SW; Service de Génétique clinique, CH de Chambéry, Chambéry, France.
NPJ Genom Med ; 6(1): 91, 2021 Nov 04.
Article en En | MEDLINE | ID: mdl-34737294
ABSTRACT
Autism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome sequence data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 18 individuals from 16 unrelated families carrying a heterozygous guanine duplication (c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (genomic location [hg38]g.50,721,512dup) affecting SHANK3, a prototypical ASD gene (0.08% of ASD-affected individuals carried the predicted p.Ala1227Glyfs*69 frameshift variant). Most probands carried de novo mutations, but five individuals in three families inherited it through somatic mosaicism. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (17/17) formally tested for ASD carried a diagnosis, there was the variable expression of core ASD features both within and between families. Defining such recurrent mutational mechanisms underlying an ASD outcome is important for genetic counseling and early intervention.
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Texto completo: 1 Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: NPJ Genom Med Año: 2021 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: NPJ Genom Med Año: 2021 Tipo del documento: Article País de afiliación: Canadá