title: MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways.
abstract: MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types.
authors: Department of Neurology, Pediatrics, and Biomedical Genetics, Center for Neural Development & Disease, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA. Alex_Paciorkowski@urmc.rochester.edu
authors: Alex R
authors: AR
authors: Paciorkowski
authors: Ryan N
authors: RN
authors: Traylor
authors: Jill A
authors: JA
authors: Rosenfeld
authors: Jacqueline M
authors: JM
authors: Hoover
authors: Catharine J
authors: CJ
authors: Harris
authors: Susan
authors: S
authors: Winter
authors: Yves
authors: Y
authors: Lacassie
authors: Martin
authors: M
authors: Bialer
authors: Allen N
authors: AN
authors: Lamb
authors: Roger A
authors: RA
authors: Schultz
authors: Elizabeth
authors: E
authors: Berry-Kravis
authors: Brenda E
authors: BE
authors: Porter
authors: Marni
authors: M
authors: Falk
authors: Anu
authors: A
authors: Venkat
authors: Rena J
authors: RJ
authors: Vanzo
authors: Julie S
authors: JS
authors: Cohen
authors: Ali
authors: A
authors: Fatemi
authors: William B
authors: WB
authors: Dobyns
authors: Lisa G
authors: LG
authors: Shaffer
authors: Blake C
authors: BC
authors: Ballif
authors: Eric D
authors: ED
authors: Marsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics*; D007223:Infant; D007395:Interneurons / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009415:Nerve Net / Q000254:growth & development*; D010641:Phenotype; D055815:Young Adult
chemical_list: D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human
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