{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:44:15Z","timestamp":1785156255652,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["U54HD061222"],"award-info":[{"award-number":["U54HD061222"]}]},{"name":"National Institutes of Health","award":["P50HD103537"],"award-info":[{"award-number":["P50HD103537"]}]},{"name":"National Institutes of Health","award":["UL1TR0030396"],"award-info":[{"award-number":["UL1TR0030396"]}]},{"name":"National Institutes of Health","award":["UL1TR002243"],"award-info":[{"award-number":["UL1TR002243"]}]},{"name":"UAB Clinical Translational Research Center","award":["U54HD061222"],"award-info":[{"award-number":["U54HD061222"]}]},{"name":"UAB Clinical Translational Research Center","award":["P50HD103537"],"award-info":[{"award-number":["P50HD103537"]}]},{"name":"UAB Clinical Translational Research Center","award":["UL1TR0030396"],"award-info":[{"award-number":["UL1TR0030396"]}]},{"name":"UAB Clinical Translational Research Center","award":["UL1TR002243"],"award-info":[{"award-number":["UL1TR002243"]}]},{"name":"Vanderbilt University Medical Center Clinical Translational Research Center","award":["U54HD061222"],"award-info":[{"award-number":["U54HD061222"]}]},{"name":"Vanderbilt University Medical Center Clinical Translational Research Center","award":["P50HD103537"],"award-info":[{"award-number":["P50HD103537"]}]},{"name":"Vanderbilt University Medical Center Clinical Translational Research Center","award":["UL1TR0030396"],"award-info":[{"award-number":["UL1TR0030396"]}]},{"name":"Vanderbilt University Medical Center Clinical Translational Research Center","award":["UL1TR002243"],"award-info":[{"award-number":["UL1TR002243"]}]},{"name":"Children\u2019s Hospital Colorado Foundation Ponzio Family Chair in Neurology Research","award":["U54HD061222"],"award-info":[{"award-number":["U54HD061222"]}]},{"name":"Children\u2019s Hospital Colorado Foundation Ponzio Family Chair in Neurology Research","award":["P50HD103537"],"award-info":[{"award-number":["P50HD103537"]}]},{"name":"Children\u2019s Hospital Colorado Foundation Ponzio Family Chair in Neurology Research","award":["UL1TR0030396"],"award-info":[{"award-number":["UL1TR0030396"]}]},{"name":"Children\u2019s Hospital Colorado Foundation Ponzio Family Chair in Neurology Research","award":["UL1TR002243"],"award-info":[{"award-number":["UL1TR002243"]}]},{"name":"International Rett Syndrome Foundation","award":["U54HD061222"],"award-info":[{"award-number":["U54HD061222"]}]},{"name":"International Rett Syndrome Foundation","award":["P50HD103537"],"award-info":[{"award-number":["P50HD103537"]}]},{"name":"International Rett Syndrome Foundation","award":["UL1TR0030396"],"award-info":[{"award-number":["UL1TR0030396"]}]},{"name":"International Rett Syndrome Foundation","award":["UL1TR002243"],"award-info":[{"award-number":["UL1TR002243"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different between the cohorts, but specific clinical features varied between the cohorts. Overall severity from first to last visit increased in the younger cohort but not in the older cohort. While some specific clinical features in the older cohort were stable from the first to the last visit, others showed improvement or worsening. These data do not support the hypothesis that mild MECP2 variants or less overall severity leads to increased longevity in RTT but demonstrate that clinical features change with increasing age in adults with RTT. Additional work is needed to understand disease progression in adults with RTT.<\/jats:p>","DOI":"10.3390\/genes15081107","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T06:28:51Z","timestamp":1724308131000},"page":"1107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical Features and Disease Progression in Older Individuals with Rett Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-5872","authenticated-orcid":false,"given":"Jeffrey L.","family":"Neul","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6969-5061","authenticated-orcid":false,"given":"Timothy A.","family":"Benke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Neurology and Pharmacology, University of Colorado School of Medicine, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Suter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin C.","family":"Ryther","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-2696","authenticated-orcid":false,"given":"David N.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Feyma","sequence":"additional","affiliation":[{"name":"Gillette Children\u2019s Specialty Healthcare, St Paul, MN 55101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9095-6174","authenticated-orcid":false,"given":"Arthur","family":"Beisang","sequence":"additional","affiliation":[{"name":"Gillette Children\u2019s Specialty Healthcare, St Paul, MN 55101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heydemann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarika U.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitha","family":"Ananth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K.","family":"Percy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"ref_1","first-page":"723","article-title":"On a Unusual Brain Atrophy Syndrome in Hyperammonemia in Childhood","volume":"116","author":"Rett","year":"1966","journal-title":"Wien. 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