By Rachel Miller, School of Medicine

One UNM scientist is leading research on a genetic condition among autism spectrum disorders known as Rett Syndrome—a devastating neurological disorder diagnosed almost exclusively in baby girls.

photo credit - Barry Staver UNM's Doctor Xinyu Zhao

Development in girls with Rett Syndrome is normal until they are between 6 and 18 months old, when their growth and maturation suddenly diminish over a period of days or weeks. This rapid regression can include a wide range of neurological defects such as mental retardation, autistic behavior, seizures, breathing problems, and loss of muscle control. After this initial deterioration, patients often survive into adulthood with no further degeneration.

More than 80 percent of Rett cases are caused by mutations in the MECP2 gene on the X chromosome. The severity of Rett is dependent on the type of mutations and X-chromosome inactivation patterns in the patients. Xinyu Zhao, PhD, assistant professor in UNM’s Department of Neurosciences, is examining the precise role that protein MeCP2 plays in brain development. Using genetic mutant mice as model, she and her graduate student, Richard Smrt, found that in the absence of a functional MeCP2 protein, the neurons in the brain have altered expression of critical factors involved in neuronal maturation and neurons do reach full maturity.

MeCP2 belongs to a family of methyl-CpG binding proteins that, by binding to methylated DNA, repress gene transcription through epigenetic mechanism. Recently, abnormal expression and mutations of MeCP2 were found in some other neurological disorders such as autism and Angelman syndrome, suggesting common molecular mechanisms underlie these complex diseases. In addition, Dr Zhao’s group has found that the mutation of MBD1, a protein belongs to the same family of MeCP2, leads to autistic phenotypes in mouse models. Mutation of MBD1 has been found in one family of autistic patients. Dr. Zhao hopes that the study of these two proteins will unlock answers to many other neurodevelopmental conditions such as autism, bipolar disorder, and schizophrenia, for which genetic components are suspected but not yet identified.


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