Phenotypic analysis of interstitial duplication
15q11-q13 patients

Lawrence T. Reiter
Department of Neurology
University of Tennessee Health Science Center
Memphis, TN
lreiter@utmem.edu
Phone: 901-448-2635

The role of UBE3A in autism spectrum disorders.
My lab studies a protein called UBE3A.  The primary role of UBE3A is to target other proteins for degradation by the ubiquitin proteasome system.  It has been known for some time now that maternally inherited mutations in UBE3A or deletions encompassing UBE3A can cause a severe mental retardation disorder called Angelman syndrome.  More recently several groups have shown that interstitial duplication 15q patients preferentially inherit this duplication from their mothers.  We believe that this maternal preference is a clear indication that duplication of the UBE3A gene is responsible for at least some aspects of the autism phenotype in these individuals.  In a recent publication Dr. Carolyn Schanen has shown that at least some 15q duplication patients have elevated levels of UBE3A protein in their lymphocytes.  Our hypothesis is that the proteins regulated by UBE3A are detrimentally affected by this elevation in UBE3A levels resulting in an autism phenotype.

What is the purpose of this study?
The focus of this study is to do an in depth analysis of interstitial duplication 15q patients in order to gain insights into which characteristics of this type of autism may be the result of UBE3A mis-regulation. The study will involve three days of tests that include a neurological exam, a blood draw, an EEG, language, and neuropsychiatric evaluations.  It may be necessary to sedate patients for part or all of the EEG, but this would be the only type of medication given during the study.  We hope that by analyzing individuals with this small 15q duplication, we will be able to better understand which characteristics of autism are related directly to the up regulation of UBE3A levels.

Who do we want to recruit for this study?
Our goal is to recruit 20 interstitial duplication 15q11-q13 patients for this study.  Since our focus is primarily on the phenotypic effects of the UBE3A gene, we are not recruiting patients with the larger isodicentric 15q duplication as the additional genes in this duplication will contribute to complicate the phenotypic analysis.  Also, since this particular duplication is rare, the study is open to patients of all age groups.  We will also be recruiting 20-40 non-duplication autism controls for the study.  This pilot study is currently being funded through the Shainberg Neuroscience Fund from Le Bonheur Children’s Hospital. Although we do have some travel funds available, we can only provide these on a case by case basis due to funding limitations.

Who do I contact?
Families who wish to learn more about this study please contact Dr. Lawrence T. Reiter in the Department of Neurology at the University of Tennessee Health Science Center, Memphis, TN. 
E-mail: lreiter@utmem.edu. 
Phone: 901-448-2635.