{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:59:50Z","timestamp":1772801990929,"version":"3.50.1"},"reference-count":92,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","award":["643417"],"award-info":[{"award-number":["643417"]}],"id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Huntingtin (<jats:italic>HTT<\/jats:italic>) gene contains a CAG repeat in exon 1, whose expansion beyond 39 repeats consistently leads to Huntington's disease (HD), whereas normal\u2010to\u2010intermediate alleles seemingly modulate brain structure, function and behavior. The role of the CAG repeat in Autism Spectrum Disorder (ASD) was investigated applying both family\u2010based and case\u2013control association designs, with the SCA3 repeat as a negative control. Significant overtransmission of \u201clong\u201d CAG alleles (\u226517 repeats) to autistic children and of \u201cshort\u201d alleles (\u226416 repeats) to their unaffected siblings (all<jats:italic>p<\/jats:italic>\u2009&lt;\u200910<jats:sup>\u22125<\/jats:sup>) was observed in 612 ASD families (548 simplex and 64 multiplex). Surprisingly, both 193 population controls and 1,188 neurological non\u2010HD controls have significantly lower frequencies of \u201cshort\u201d CAG alleles compared to 185 unaffected siblings and higher rates of \u201clong\u201d alleles compared to 548 ASD patients from the same families (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05\u2013.001). The SCA3 CAG repeat displays no association. \u201cShort\u201d HTT alleles seemingly exert a protective effect from clinically overt autism in families carrying a genetic predisposition for ASD, while \u201clong\u201d alleles may enhance autism risk. Differential penetrance of autism\u2010inducing genetic\/epigenetic variants may imply atypical developmental trajectories linked to HTT functions, including excitation\/inhibition imbalance, cortical neurogenesis and apoptosis, neuronal migration, synapse formation, connectivity and homeostasis.<\/jats:p>","DOI":"10.1002\/ajmg.b.32806","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T21:05:14Z","timestamp":1594501514000},"page":"341-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Huntingtin gene<scp>CAG<\/scp>repeat size affects autism risk: Family\u2010based and case\u2013control association study"],"prefix":"10.1002","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4024-3368","authenticated-orcid":false,"given":"Ignazio Stefano","family":"Piras","sequence":"first","affiliation":[{"name":"Neurogenomics Division The Translational Genomics Research Institute Phoenix Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Picinelli","sequence":"additional","affiliation":[{"name":"Mafalda Luce Center for Pervasive Developmental Disorders Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"Iennaco","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano Milan Italy"},{"name":"Istituto Nazionale di Genetica Molecolare \u201cRomeo ed Enrica Invernizzi\u201d Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Baccarin","sequence":"additional","affiliation":[{"name":"Mafalda Luce Center for Pervasive Developmental Disorders Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Castronovo","sequence":"additional","affiliation":[{"name":"Mafalda Luce Center for Pervasive Developmental Disorders Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Tomaiuolo","sequence":"additional","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d, \u201cGaetano Martino\u201d University Hospital University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Cucinotta","sequence":"additional","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d, \u201cGaetano Martino\u201d University Hospital University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Ricciardello","sequence":"additional","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d, \u201cGaetano Martino\u201d University Hospital University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Turriziani","sequence":"additional","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d, \u201cGaetano Martino\u201d University Hospital University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Nanetti","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Mariotti","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Gellera","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Lintas","sequence":"additional","affiliation":[{"name":"Unit of Child and Adolescent NeuroPsychiatry &amp; 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