ArticleOrphanet journal of rare diseases2013
A synonymous change, p.Gly16Gly in MECP2 Exon 1, causes a cryptic splice event in a Rett syndrome patient.
Article in Orphanet journal of rare diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 26 citations in OpenAlex.
- Splice-site variants in neurology: from molecular mechanisms to clinical interpretation - a focused review.Neurogenetics · 2026Review
- MECP2 mutations disrupt pluripotent stem cell fate through remodeling of the three-dimensional genome.Cell death & disease · 2026Article
- A practical framework for predicting splicing single nucleotide variants in exome sequencing.NAR genomics and bioinformatics · 2025Article
- Methyl-CpG-Binding Protein 2 Emerges as a Central Player in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.Cellular and molecular neurobiology · 2023Review
- Analysis of the genotype-phenotype correlation of MYO15A variants in Chinese non-syndromic hearing loss patients.BMC medical genomics · 2022Article
- Evidence in disease and non-disease contexts that nonsense mutations cause altered splicing via motif disruption.Nucleic acids research · 2021Article
- MeCP2: The Genetic Driver of Rett Syndrome Epigenetics.Frontiers in genetics · 2021Review
- Systematic Analysis of Splice-Site-Creating Mutations in Cancer.Cell reports · 2018Article
- MeCP2_E1 N-terminal modifications affect its degradation rate and are disrupted by the Ala2Val Rett mutation.Human molecular genetics · 2017Article
- Settling the score: variant prioritization and Mendelian disease.Nature reviews. Genetics · 2017Review
- From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2.Scientific reports · 2016Article
- Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).Molecular neurobiology · 2016Review
- The functional relevance of somatic synonymous mutations in melanoma and other cancers.Pigment cell & melanoma research · 2015Review
- Rett syndrome and MeCP2.Neuromolecular medicine · 2014Review
- Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.PloS one · 2014Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in MECP2 are the main cause of Rett Syndrome. To date, no pathogenic synonymous MECP2 mutation has yet been identified. Here, we investigated a de novo synonymous variant c.48C>T (p.Gly16Gly) identified in a girl presenting with a typical RTT phenotype.
methodsIn silico analyses to predict the effects of sequence variation on mRNA splicing were employed, followed by sequencing and quantification of lymphocyte mRNAs from the subject for splice variants MECP2_E1 and MECP2_E2.
resultsAnalysis of mRNA confirmed predictions that this synonymous mutation activates a splice-donor site at an early position in exon 1, leading to a deletion (r.[=, 48_63del]), codon frameshift and premature stop codon (p.Glu17Lysfs*16) for MECP2_E1. For MECP2_E2, the same premature splice site is used, but as this is located in the 5'untranslated region, no effect on the amino acid sequence is predicted. Quantitative analysis that specifically measured this cryptic splice variant also revealed a significant decrease in the quantity of the correct MECP2_E1 transcript, which indicates that this is the etiologically significant mutation in this patient.
conclusionThese findings suggest that synonymous variants of MECP2 as well as other known disease genes-and de novo variants in particular- should be re-evaluated for potential effects on splicing.
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