{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T07:46:45Z","timestamp":1772696805330,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T00:00:00Z","timestamp":1324944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The overwhelming majority of Rett syndrome cases are caused by mutations in the gene <jats:italic>MECP2<\/jats:italic>. MECP2 has two isoforms, termed MECP2_e1 and MECP2_e2, which differ in their N\u2010terminal amino acid sequences. A growing body of evidence has indicated that MECP2_e1 may be the etiologically relevant isoform in Rett Syndrome based on its expression profile in the brain and because, strikingly, no mutations have been discovered that affect MECP2_e2 exclusively. In this study we sought to characterize four classical Rett patients with mutations that putatively affect only the MECP2_e1 isoform. Our hypothesis was that the classical Rett phenotype seen here is the result of disrupted MECP2_e1 expression, but with MECP2_e2 expression unaltered. We used quantitative reverse transcriptase PCR to assay mRNA expression for each isoform independently, and used cytospinning methods to assay total MECP2 in peripheral blood lymphocytes (PBL). In the two Rett patients with identical 11\u2009bp deletions within the coding portion of exon 1, <jats:italic>MECP2_e2<\/jats:italic> levels were unaffected, whilst a significant reduction of <jats:italic>MECP2_e1<\/jats:italic> levels was detected. In two Rett patients harboring mutations in the exon 1 start codon, <jats:italic>MECP2_e1<\/jats:italic> and <jats:italic>MECP2_e2<\/jats:italic> mRNA amounts were unaffected. In summary, we have shown that patients with exon 1 mutations transcribe normal levels of <jats:italic>MECP2_e2<\/jats:italic> mRNA, and most PBL are positive for MeCP2 protein, despite them theoretically being unable to produce the MECP2_e1 isoform, and yet still exhibit the classical RTT phenotype. Altogether, our work further supports our hypothesis that MECP2_e1 is the predominant isoform involved in the neuropathology of Rett syndrome. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.32015","type":"journal-article","created":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T13:43:38Z","timestamp":1324993418000},"page":"210-216","source":"Crossref","is-referenced-by-count":22,"title":["Mutations in <i>MECP2<\/i> exon 1 in classical rett patients disrupt <i>MECP2_e1<\/i> transcription, but not transcription of <i>MECP2_e2<\/i>"],"prefix":"10.1002","volume":"159B","author":[{"given":"Peter 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