Abstract: Series 109, Lecture 5
The Harvey Lectures Series 109 (2013—2014)
previous lecture | next lecture
Lecture #5: Thursday, March 20, 2014 — Watch Video of Lecture
A Neural Tipping Point: MeCP2 and Neuropsychiatric Disorders
Huda Y Zoghbi, MD
Professor, Departments of Pediatrics, Molecular and Human Genetics,
Neurology, and Neuroscience, Baylor College of Medicine
Ralph D Feigin, MD, Endowed Chair
Director, Jan & Dan Duncan Neurological Research Institute, Texas Children’s Hospital
Investigator, Howard Hughes Medical Institute
Howard Hughes Medical Institute, Baylor College of Medicine
Houston, Texas
I owe my decision to pursue research to a five-year-old girl. I was a resident in pediatric neurology, and she was an enigma: she had achieved all her early developmental milestones only to lose them all, one by one. She turned out to have Rett Syndrome, a rare disorder that strikes in the second year of life, robbing children of acquired linguistic, and social skills and producing stereotypic hand motions, autistic behaviors, seizures, and motor problems. My lab’s discovery, years later, that Rett syndrome is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) opened up a new field of research into disorders of epigenetic regulation, which in turn is influencing the field of neuropsychiatric disorders. Mutations in MECP2 produce anything from severe neonatal encephalopathy in males to juvenile-onset schizophrenia or bipolar disease with accompanying movement abnormalities; duplications spanning MECP2 cause (in males) a neurological disorder that begins with autism and progresses to a Rett-like syndrome and (in carrier females) anxiety and depression. Human studies and mouse models have shown that the brain is exquisitely sensitive to MeCP2 levels, though its precise molecular functions remain to be fully elucidated. Studying the role of the protein in various neuronal subtypes, however, sheds light on the contributions of various networks to the wide variety of MeCP2-related phenotypes.