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Refining the phenotype associated with MEF2C point mutations
Thierry Bienvenu1, Bertrand Diebold, Jamel Chelly
1CNRS UMR 8104, Institut Cochin, Laboratoire de Génétique des Maladies Neurodéveloppementales, Université Paris Descartes, Paris, France. thierry.bienvenu@inserm.fr
Abstract:
Up to now, only five-point mutations in the MEF2C gene have been described in patients with severe mental retardation with absent speech, limited walking abilities, epilepsy, and lack of gross malformations. In brain, MEF2C is essential for early neurogenesis, neuronal migration, and differentiation. Here, we present a new patient with severe mental retardation, epilepsy, and hand stereotypies associated with a novel MEF2C frameshift mutation c.457delA. The purpose of this work was to clarify criteria for the selection of patients with severe intellectual disability to screen for deficiency in the MEF2C gene. By combining the clinical data of all patients with MEF2C point mutations published so far with the phenotype of our patient, a targeted search for MEF2C mutations could be applied to patients with a severe intellectual deficiency associated with absence of language and hypotonia, strabismus, and epilepsy (started after 6 months, often well controlled by valproate).
Insights
Researchers identified a new MEF2C gene mutation in a patient with severe intellectual disability and epilepsy. This finding helps refine criteria for screening patients with severe intellectual disability for MEF2C gene deficiency.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Mutations in the MEF2C gene are linked to severe intellectual disability, absent speech, motor deficits, and epilepsy.
- MEF2C plays a crucial role in brain development, including neurogenesis, neuronal migration, and differentiation.
Purpose of the Study:
- To establish criteria for selecting patients with severe intellectual disability for MEF2C gene screening.
- To characterize the phenotype associated with novel MEF2C mutations.
Main Methods:
- Clinical data from a new patient with a frameshift MEF2C mutation (c.457delA) were analyzed.
- Phenotypic data from previously reported patients with MEF2C point mutations were combined with the new case.
- A targeted search strategy for MEF2C mutations was developed based on combined clinical data.
Main Results:
- A novel MEF2C frameshift mutation (c.457delA) was identified in a patient presenting with severe intellectual disability, epilepsy, and hand stereotypies.
- The study identified a specific phenotype associated with MEF2C deficiency, including severe intellectual deficiency, absence of language, hypotonia, strabismus, and early-onset epilepsy.
- Epilepsy in these patients often begins after six months of age and is frequently well-controlled with valproate.
Conclusions:
- The study refines the clinical criteria for suspecting MEF2C gene mutations in patients with severe intellectual disability.
- Identifying specific clinical features aids in the targeted screening for MEF2C deficiency, improving diagnostic yield.
- This work expands the understanding of MEF2C-related neurodevelopmental disorders and associated phenotypes.
