FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family
Abstract Background Children with autism spectrum disorder (ASD) display impressive clinical heterogeneity, also involving treatment response. Genetic variants can contribute to explain this large interindividual phenotypic variability. Methods Array‐CGH (a‐CGH) and whole genome sequencing (WGS) wer...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1373 |
| _version_ | 1797301163911020544 |
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| author | Francesca Cucinotta Arianna Ricciardello Laura Turriziani Giorgia Calabrese Marilena Briguglio Maria Boncoddo Fabiana Bellomo Pasquale Tomaiuolo Silvia Martines Marianna Bruschetta Francesca La Fauci Belponer Tiziana Di Bella Costanza Colombi Marco Baccarin Chiara Picinelli Paola Castronovo Carla Lintas Roberto Sacco Thomas Biederer Barbara Kellam Stephen W. Scherer Antonio M. Persico |
| author_facet | Francesca Cucinotta Arianna Ricciardello Laura Turriziani Giorgia Calabrese Marilena Briguglio Maria Boncoddo Fabiana Bellomo Pasquale Tomaiuolo Silvia Martines Marianna Bruschetta Francesca La Fauci Belponer Tiziana Di Bella Costanza Colombi Marco Baccarin Chiara Picinelli Paola Castronovo Carla Lintas Roberto Sacco Thomas Biederer Barbara Kellam Stephen W. Scherer Antonio M. Persico |
| author_sort | Francesca Cucinotta |
| collection | DOAJ |
| description | Abstract Background Children with autism spectrum disorder (ASD) display impressive clinical heterogeneity, also involving treatment response. Genetic variants can contribute to explain this large interindividual phenotypic variability. Methods Array‐CGH (a‐CGH) and whole genome sequencing (WGS) were performed on a multiplex family with two small children diagnosed with ASD at 17 and 18 months of age. Both brothers received the same naturalistic intervention for one year according to the Early Start Denver Model (ESDM), applied by the same therapists, yielding dramatically different treatment outcomes. Results The older sibling came out of the autism spectrum, while the younger sibling displayed very little, in any, improvement. This boy was subsequently treated applying a structured Early Intensive Behavioral Intervention paired with Augmentative Alternative Communication, which yielded a partial response within another year. The ESDM nonresponsive child carries a novel maternally inherited 65 Kb deletion at chr. 13q32.2 spanning FARP1. Farp1 is a synaptic scaffolding protein, which plays a significant role in neural plasticity. Conclusion These results represent a paradigmatic example of the heuristic potential of genetic markers in predicting treatment response and possibly in supporting the targeted prescription of specific early intervention approaches. |
| first_indexed | 2024-03-07T23:17:30Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:17:30Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-fad1dd81389e4f15bb4c6f2937598d762024-02-21T10:24:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-09-0189n/an/a10.1002/mgg3.1373FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex familyFrancesca Cucinotta0Arianna Ricciardello1Laura Turriziani2Giorgia Calabrese3Marilena Briguglio4Maria Boncoddo5Fabiana Bellomo6Pasquale Tomaiuolo7Silvia Martines8Marianna Bruschetta9Francesca La Fauci Belponer10Tiziana Di Bella11Costanza Colombi12Marco Baccarin13Chiara Picinelli14Paola Castronovo15Carla Lintas16Roberto Sacco17Thomas Biederer18Barbara Kellam19Stephen W. Scherer20Antonio M. Persico21Interdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyDepartment of Psychiatry University of Michigan Ann Arbor MI USAMafalda Luce Center for Pervasive Developmental Disorders Milan ItalyMafalda Luce Center for Pervasive Developmental Disorders Milan ItalyMafalda Luce Center for Pervasive Developmental Disorders Milan ItalyService for Neurodevelopmental Disorders & Laboratory of Molecular Psychiatry and Neurogenetics University “Campus Bio‐Medico” Rome ItalyService for Neurodevelopmental Disorders & Laboratory of Molecular Psychiatry and Neurogenetics University “Campus Bio‐Medico” Rome ItalyDepartment of Neurology Yale University School of Medicine New Haven CT USAGenetics & Genome Biology Program Toronto CanadaGenetics & Genome Biology Program Toronto CanadaInterdepartmental Program "Autism 0‐90" "G. Martino" University Hospital of Messina Messina ItalyAbstract Background Children with autism spectrum disorder (ASD) display impressive clinical heterogeneity, also involving treatment response. Genetic variants can contribute to explain this large interindividual phenotypic variability. Methods Array‐CGH (a‐CGH) and whole genome sequencing (WGS) were performed on a multiplex family with two small children diagnosed with ASD at 17 and 18 months of age. Both brothers received the same naturalistic intervention for one year according to the Early Start Denver Model (ESDM), applied by the same therapists, yielding dramatically different treatment outcomes. Results The older sibling came out of the autism spectrum, while the younger sibling displayed very little, in any, improvement. This boy was subsequently treated applying a structured Early Intensive Behavioral Intervention paired with Augmentative Alternative Communication, which yielded a partial response within another year. The ESDM nonresponsive child carries a novel maternally inherited 65 Kb deletion at chr. 13q32.2 spanning FARP1. Farp1 is a synaptic scaffolding protein, which plays a significant role in neural plasticity. Conclusion These results represent a paradigmatic example of the heuristic potential of genetic markers in predicting treatment response and possibly in supporting the targeted prescription of specific early intervention approaches.https://doi.org/10.1002/mgg3.1373autism spectrum disorderbiomarkersFARP1neuronal plasticitytreatment outcome |
| spellingShingle | Francesca Cucinotta Arianna Ricciardello Laura Turriziani Giorgia Calabrese Marilena Briguglio Maria Boncoddo Fabiana Bellomo Pasquale Tomaiuolo Silvia Martines Marianna Bruschetta Francesca La Fauci Belponer Tiziana Di Bella Costanza Colombi Marco Baccarin Chiara Picinelli Paola Castronovo Carla Lintas Roberto Sacco Thomas Biederer Barbara Kellam Stephen W. Scherer Antonio M. Persico FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family Molecular Genetics & Genomic Medicine autism spectrum disorder biomarkers FARP1 neuronal plasticity treatment outcome |
| title | FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family |
| title_full | FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family |
| title_fullStr | FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family |
| title_full_unstemmed | FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family |
| title_short | FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family |
| title_sort | farp 1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family |
| topic | autism spectrum disorder biomarkers FARP1 neuronal plasticity treatment outcome |
| url | https://doi.org/10.1002/mgg3.1373 |
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