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First description of an unusual novel double mutation in MECP 2 co‐occurring with the m.827A>G mutation in the MT‐RNR1 gene associated with angelman‐like syndrome
Author(s) -
Kharrat Marwa,
Triki Chahnez,
Maalej Marwa,
Ncir Sihem,
Ammar Marwa,
Kammoun Fatma,
Fakhfakh Faiza
Publication year - 2019
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2019.10.002
Subject(s) - mecp2 , genetics , mutation , rett syndrome , biology , gene mutation , gene , mitochondrial dna , microbiology and biotechnology , phenotype
Mutations in Methyl‐CpG‐Binding protein 2 ( MECP2 ), located on Xq28 and encoding a methyl CpG binding protein, are commonly related to Rett syndrome. However, MECP2 mutations have already been reported in patients with neurodevelopmental abnormalities such as X‐linked mental retardation, severe neonatal encephalopathy and Angelman‐like syndrome (AS‐like). Accordingly, we report the clinical, molecular and bioinformatic analyses in a Tunisian patient with AS‐like phenotype. In fact, the direct sequencing of MECP2 and cloning essay reveals the emergence of an unusual novel double mutation, including a de novo mutation c.397C > T (p.R133C) and an inherited one c.608C > T (p.T203 M) co‐occurring in Trans . We also provide the molecular evidence of the c.608C > T 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 > G in the MT‐RNR1 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 > T in trans with c.608C > T) in MECP2 co‐occurring with the mitochondrial m.827A > G mutation in the MT‐RNR1 gene in a Tunisian patient with AS‐like. Besides, our results highlight the importance of studying MECP2 and the significance of mDNA screening in AS‐like disorder for a better understanding of its etiopathogenesis.