Category Archives: Publications

MRIs in MECP2 Duplication Syndrome

MRIThis post provides some information on MRI findings in MECP2 duplication syndrome. It is based mostly on one study by French researchers (El Chehadeh, S., Faivre, L, Mosca-Boidron , et al. 2016)

The study included findings from MRI brain scans from 30 individuals with MECP2 duplication syndrome. The sample included males and females from under one year old to 49 years old. The MECP2 duplications included short and long duplications, duplications on the X chromosome and translocations to other chromosomes. The study was designed to determine if other specific genes included in the duplicated material influenced the observed MRI findings, however, no systematic differences were found. There was some limited evidence of increased atrophy of some structures over time.

The researchers reported that 93% of the individuals studied had significant abnormal findings. Some of the most common findings included

abnormalities or underdevelopment of the corpus callosum (67% of individuals) The corpus callosum is the main connection between the right and left side of the brain. It was frequently described as poorly developed, thin, or missing.

reduced white matter volume (40% of individuals) White matter comprises the area of the brain where most connections are made.

ventricular dilatation (30% of individuals) The ventricles are hollow spaces in the brain that contain fluid

Half of the individuals studied were epileptic and almost all of those had poorly controlled seizures. There was no clear difference in brain structures  and presence or absence of seizures.

Some previous studies have reported similar findings.

One interesting finding was on head circumference. Most individuals were within normal limits, but there were some in the microcephalic range and others in the macrocephalic range.

Reference

El Chehadeh, S., Faivre, L, Mosca-Boidron , et al. (2016). A.Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients. American Journal of Medical Genetics, Part A, 170A(1):116-29. doi: 10.1002/ajmg.a.37384.

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New Research on the Role of MECP2

flaskResearch newly published in PNAS, Proceedings of the National Academy of Sciences, helps to clarify how the MeCP2 protein regulates genes, and may help provide an explanation of the role of MECP2-related disorders in autism. Researchers at Harvard University and the Washington University School of Medicine published their findings showing that MeCP2 plays a particular role in regulating very long genes in the brain. They found that MeCP2 reduced the activity of genes in proportion to the number of available sites for methylation. Therefore, the longer the gene, the greater the role of MECP2 in regulating the gene, and thus the very long genes in the brain are most sensitive to changes in levels of MeCP2.

Previous research has suggested that the function of very long genes in the brain may be a common denominator in at least many of the underlying causes  of autism. This new finding may suggest that both the underactivity of the MECP2 gene found in Rett syndrome and overactivity of the MECP2 gene found in MECP2 duplication syndrome may result in impaired responsiveness of these very long genes, potentially producing symptoms of autism. Continue reading

Touch, Autism, and MECP2

flaskResearchers at Harvard University are suggesting a new theory of autism. They are raising the possibility that atypical neurological responses to touch can play an important role in developing symptoms of autism, and suggesting that abnormal levels of MeCP2 levels in cells that respond to touch can be critical to the development of symptoms of autism.

Experiments with a number of types of genetically engineered laboratory mice, they found autistic-like behavior developed in those without MECP2 activity in touch cells, but not if normal activity was present in touch cells but not in other cells in the body. There are a number of cautions in interpreting this finding and the associated theory, but there are also a number of general observations that make this theory enticing. Continue reading

More Research on Cannabidiol & Seizures

flaskSeveral new studies provide encouraging results about the use of cannabidiol (CBD) oil to treat seizure disorders that are not controlled by other medications. Research also, however, points toward important cautions.

Already in 2016,at least nine studies have been published on CBD and seizures. Two 2016 studies, one from Israel (Tzadok et al.,, 2016) and one the United States (Devinsky et al., 2016) are generally reporting particularly encouraging results. This is not to say the others are negative, just less relevant. The two discussed here are important because they include some results Continue reading

Another Big Step Forward with CRISPR

NEW3“Using a previously undescribed approach involving single guide RNA, we successfully removed large genome rearrangement in primary cells of an individual with an X chromosome duplication including MECP2.”

Wojtal, D., Kemaladewi, D. U., Malam, Z., Abdullah, S., Wong, T. W., Hyatt, E., et al. (2016). Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders. American Journal of Human  Genetics, 98(1), 90-101.

2015 and 2016 have already been marked by some major breakthroughs in potential steps toward treatment of MECP2 Duplication Syndrome. This  report in the American Journal of Human Genetics definitely adds to collection. Continue reading

Zoghbi Lab Reversal Study

News icon25 November 2015 Today’s publication in Nature:

Yehezkel Sztainberg, Hong-mei Chen, John W. Swann, Shuang Hao, Bin Tang, Zhenyu Wu, Jianrong Tang, Ying-Wooi Wan, Zhandong Liu, Frank Rigo & Huda Y. Zoghbi (2015 November 25). Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides. Nature doi:10.1038/nature1615

Dr Zoghbi explains what they have accomplished in this video from the 401 project. Video created by Joseph Mendoza.

The  article in Nature is what families have long been waiting and hoping for. Continue reading

Recent Study on Seizures and MECP2 Duplication Syndrome

NEW3A pre-publication manuscript of a recent study provides some more information on seizure disorders in MECP2 Duplication syndrome.

This research is very consistent with the parent survey results previously reported on this blog site on March 27, 2012. However, the study also includes information on brain electrical activity. Unfortunately, it suggests that seizures in individuals with MECP2 Duplication Syndrome are associated with different patterns of electrical activity in different individuals, which may mean no single approach to treatment is likely to be successful for all individuals with the syndrome. Continue reading

Parent Survey on the Use of Cannabidiol in Intractable Epilepsy

NEW3While there  has been a lot of popular discussion of treating seizures with Cannabidiol, there have been few published studies of the results in children with seizure disorders. A study published in December 2013 in the journal Epilepsy and Behavior provides some encouraging information. While the study only surveyed a small number of participants and depended on parent perceptions rather than objectively measured data, the results were positive. Continue reading

Regression: Is it inevitable?

strEarlier this year a brief article was published on regression in MECP2 Duplication Syndrome in the Journal of Autism and Developmental Disorders.

 Peters, S.U., Hundley, R.J., Wilson, A.K., Carvalho, C.M.B.,  Lupski, J.R., & Ramocki, M.B. (2013). Brief Report: Regression Timing and Associated Features in MECP2 Duplication Syndrome. Journal of Autism and Developmental Disorders, Published online, 2 March 2013. Continue reading

5hmC and A new role for MECP2?

cell5-hydroxymethylcytosine (5hmC) is a substance found in many cells and particularly in the brain cells. Although there is much that remains unknown about it, it has been receiving a lot of attention from researchers because of its apparent pole in epigenetics. Epigenetics refers to the process by which gene expression is modified by non-genetic factors, such as external environmental influences.  For example, our DNA may determine the likelihood that we we will develop high blood pressure later in life, but this can be modified by a lack of an adequate diet in childhood or even our during our mother’s pregnancy. Our DNA is not altered but some genes may be “turned up” and others “turned down” by our other factors.  Exactly how these processes work is currently a major research area for many researchers, and  some researchers believe that 5hmC may be an important piece of the puzzle. Continue reading