{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:03:23Z","timestamp":1784952203382,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Higher Education and the Scientific Research in Tunisia"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Mutations in <jats:italic>Methyl\u2010CpG\u2010Binding protein 2<\/jats:italic> (<jats:italic>MECP2<\/jats:italic>), located on Xq28 and encoding a methyl CpG binding protein, are commonly related to Rett syndrome. However, <jats:italic>MECP2<\/jats:italic> mutations have already been reported in patients with neurodevelopmental abnormalities such as X\u2010linked mental retardation, severe neonatal encephalopathy and Angelman\u2010like syndrome (AS\u2010like). Accordingly, we report the clinical, molecular and bioinformatic analyses in a Tunisian patient with AS\u2010like phenotype. In fact, the direct sequencing of <jats:italic>MECP2<\/jats:italic> and cloning essay reveals the emergence of an unusual novel double mutation, including a de novo mutation c.397C\u202f&gt;\u202fT (p.R133C) and an inherited one c.608C\u202f&gt;\u202fT (p.T203\u202fM) co\u2010occurring <jats:italic>in Trans<\/jats:italic>. We also provide the molecular evidence of the c.608C\u202f&gt;\u202fT transmission to the patient which was present in her father at somatic mosaicism state. To gain insight into the molecular basis of this disorder, we undertook, for the first time, a whole mitochondrial genome mutational analysis. Thus, the results showed the presence of several variations and a homoplasmic mutation m.827A\u202f&gt;\u202fG in the <jats:italic>MT\u2010RNR1<\/jats:italic> gene, leading to the disruption of the 12S rRNA secondary structure. Our report is considered as the first to describe an unusual novel double mutation (c.397C\u202f&gt;\u202fT <jats:italic>in trans<\/jats:italic> with c.608C\u202f&gt;\u202fT) in <jats:italic>MECP2<\/jats:italic> co\u2010occurring with the mitochondrial m.827A\u202f&gt;\u202fG mutation in the <jats:italic>MT\u2010RNR1<\/jats:italic> gene in a Tunisian patient with AS\u2010like. Besides, our results highlight the importance of studying <jats:italic>MECP2<\/jats:italic> and the significance of mDNA screening in AS\u2010like disorder for a better understanding of its etiopathogenesis.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2019.10.002","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T17:06:36Z","timestamp":1571677596000},"page":"37-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["First description of an unusual novel double mutation in <i>MECP<\/i>2 co\u2010occurring with the m.827A&gt;G mutation in the <i>MT\u2010RNR1<\/i> gene associated with angelman\u2010like syndrome"],"prefix":"10.1002","volume":"79","author":[{"given":"Marwa","family":"Kharrat","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Functional Genetics Faculty of Science of Sfax University of Sfax Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chahnez","family":"Triki","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Neurology research (UR12ES 16) C.H.U. 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