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Most of RTT\u2010causing variants in\n                    <jats:italic>MECP2<\/jats:italic>\n                    are\n                    <jats:italic>de novo<\/jats:italic>\n                    and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed\n                    <jats:italic>MECP2<\/jats:italic>\n                    variants. Statistical analyses are performed using Student\n                    <jats:italic>t<\/jats:italic>\n                    \u2010test, single factor analysis of variance (ANOVA), and multi\u2010factor regression. No significant difference is observed in parental ages of RTT probands compared to that of the general population. A small increase in parental ages is observed in participants with missense variants compared to those with nonsense variants. When we evaluate the association between clinical severity and parental ages by multiple regression analysis, there is no clear association between clinical severity and parental ages. Advanced parental ages do not appear to be a risk factor for RTT, and do not contribute to the clinical severity in individuals with RTT.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63396","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T09:52:59Z","timestamp":1695894779000},"page":"160-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Parental age effects and Rett syndrome"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-7585","authenticated-orcid":false,"given":"Xiaolan","family":"Fang","sequence":"first","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Baggett","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1067-2807","authenticated-orcid":false,"given":"Raymond C.","family":"Caylor","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K.","family":"Percy","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-5872","authenticated-orcid":false,"given":"Jeffrey L.","family":"Neul","sequence":"additional","affiliation":[{"name":"Vanderbilt Kennedy Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane B.","family":"Lane","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Glaze","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6969-5061","authenticated-orcid":false,"given":"Tim A.","family":"Benke","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Children's Hospital Colorado\u2010Aurora  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-0902","authenticated-orcid":false,"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen J.","family":"Motil","sequence":"additional","affiliation":[{"name":"Vanderbilt Kennedy Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy O.","family":"Barrish","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran E.","family":"Annese","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-0792","authenticated-orcid":false,"given":"Steven A.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_7_3_1","first-page":"175","article-title":"The effect of parental age on rates of mutation for hemophilia and evidence for differing mutation rates for hemophilia A and B","volume":"20","author":"Barrai I.","year":"1968","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000304752.50773.ec"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072553"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0711-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2005.03.018"},{"key":"e_1_2_7_8_1","first-page":"1076","article-title":"Parent\u2010of\u2010origin effects in multiple endocrine neoplasia type 2B","volume":"55","author":"Carlson K. 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