{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:08:09Z","timestamp":1767852489268,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rett (RTT) syndrome, a neurodevelopmental disorder caused by pathogenic variation in the <jats:italic>MECP2<\/jats:italic> gene, is characterized by developmental regression, loss of purposeful hand movements, stereotypic hand movements, abnormal gait, and loss of spoken language. Due to the X\u2010linked inheritance pattern, RTT is typically limited to females. Recent studies revealed somatic mosaicism in <jats:italic>MECP2<\/jats:italic> in male patients with RTT\u2010like phenotypes. While detecting mosaic variation using Sanger sequencing is theoretically possible for mosaicism over ~15%\u201320%, several variables, including efficiency of PCR, background noise, and\/or human error, contribute to a low detection rate using this technology. Mosaic variants in two males were detected by next generation sequencing (NGS; Case 1) and by Sanger re\u2010sequencing (Case 2). Both had targeted digital PCR (dPCR) to confirm the variants. In this report, we present two males with classic RTT syndrome in whom we identified pathogenic variation in the <jats:italic>MECP2<\/jats:italic> gene in the mosaic state (c.730C\u2009&gt;\u2009T (p.Gln244*) in Patient 1 and c.397C\u2009&gt;\u2009T (p.Arg133Cys) in Patient 2). In addition, estimates and measures of mosaic variant fraction were surprisingly similar between Sanger sequencing, NGS, and dPCR. The mosaic state of these variants contributed to a lengthy diagnostic odyssey for these patients. While NGS and even Sanger sequencing may be viable methods of detecting mosaic variation in DNA or RNA samples, applying targeted dPCR to supplement these sequencing technologies would provide confirmation of somatic mosaicism and mosaic fraction.<\/jats:p>","DOI":"10.1002\/ajmg.a.62913","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T08:24:31Z","timestamp":1659601471000},"page":"2988-2998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mosaicism of common pathogenic <scp><i>MECP2<\/i><\/scp> variants identified in two males with a clinical diagnosis of <scp>Rett<\/scp> syndrome"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-8796","authenticated-orcid":false,"given":"Jessica A.","family":"Cooley Coleman","sequence":"first","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina 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