MECP2

About MECP2

MECP2 on chromosome Xq28 encodes methyl CpG binding protein 2, a chromatin protein that binds methylated DNA and is especially abundant in mature neurons, where it regulates the expression of many genes. Loss of function variants cause Rett syndrome, an X linked dominant neurodevelopmental disorder that mainly affects girls, since most affected males with similar variants have a severe neonatal encephalopathy. The link to MECP2 was discovered in 1999 by Huda Zoghbi and colleagues, and the syndrome is named after the Austrian physician Andreas Rett, who described it in 1966. Rett syndrome follows a characteristic course: apparently normal early development is followed in the first or second year of life by regression, with loss of speech and purposeful hand use, stereotyped hand wringing or clapping movements, slowing of head growth, gait abnormalities, breathing irregularities, seizures, and autistic features. Many affected girls survive into adulthood with substantial care needs. MECP2 duplication syndrome, mainly in boys, causes severe intellectual disability, hypotonia, seizures, and recurrent infections, showing that the dosage of this protein must be tightly controlled. Experiments in mice showed that restoring MECP2 can reverse symptoms. Trofinetide was approved in 2023 as the first treatment for Rett syndrome, and gene therapies are in clinical trials.