Refining the phenotype associated with MEF2C haploinsufficiency

• Published in: Clinical genetics Vol. 78; no. 5; pp. 471 - 477
• Main Authors: Novara, F, Beri, S, Giorda, R, Ortibus, E, Nageshappa, S, Darra, F, Dalla Bernardina, B, Zuffardi, O, Van Esch, H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Wiley-Blackwell
• Subjects: aCGH; Adolescent; Autism; Bernardina; Biological and medical sciences; Child Development Disorders, Pervasive - genetics; Child, Preschool; chromosome 5q14.3; Classical genetics, quantitative genetics, hybrids; Epilepsies, Myoclonic - genetics; Epilepsy; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Haploinsufficiency; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Human; Humans; Infant; Intellectual Disability - genetics; MADS Domain Proteins - genetics; Male; Medical genetics; Medical sciences; MEF2 Transcription Factors; MEF2C; Mental retardation; microdeletion; Molecular and cellular biology; Myogenic Regulatory Factors - genetics; Nervous system (semeiology, syndromes); Neurology; Phenotype; Sequence Deletion; severe mental retardation; Genetic mapping; Human; Microdeletion; Nervous system diseases; MEF2C; Epilepsy; severe mental retardation; Developmental disorder; Chromosome B5; Mental retardation; aCGH; Cerebral disorder; Phenotype; haploinsufficiency; Central nervous system disease; Intellectual deficiency; chromosome 5q 14.3; Genetics; Severe
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01413.x

Novara F, Beri S, Giorda R, Ortibus E, Nageshappa S, Darra F, dalla Bernardina B, Zuffardi O, Van Esch H. Refining the phenotype associated with MEF2C haploinsufficiency. Recently, submicroscopic deletions of the 5q14.3 region have been described in patients with severe mental retardation (MR), stereotypic movements, epilepsy and cerebral malformations. Further delineation of a critical region of overlap in these patients pointed to MEF2C as the responsible gene. This finding was further reinforced by the identification of a nonsense mutation in a patient with a similar phenotype. In brain, MEF2C is essential for early neurogenesis, neuronal migration and differentiation. Here we present two additional patients with severe MR, autism spectrum disorder and epilepsy, carrying a very small deletion encompassing the MEF2C gene. This finding strengthens the role of this gene in severe MR, and enables further delineation of the clinical phenotype.