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Enrique Villacres MD

Associate Professor

enrique@u.washington.edu
Phone: (206) 744-8672
Fax: (206) 731-8615

Harborview Medical Center
325 Ninth Ave, Room PS-5009
Box 359911
Seattle, WA 98104
Link to CV

Division
Office of Chair and Faculty and Staff Services


Board Certification
American Board of Psychiatry and Neurology

Bio

The goal of my research is to identify autism-causing genes. Autism is a neurodevelopmental disorder of brain function characterized by abnormal or impaired development in social interaction and communication, accompanied by markedly restricted repertoire of activity and interests. Both family and twin studies strongly support a genetic basis for autism. Our approach to identifying disease-causing genes takes advantage of the finding that a small number of patients with autism also have abnormal chromosomes. Each chromosome contains from a few hundred to several thousand genes. A gene can be disrupted when a chromosome breaks and exchanges a piece with another chromosome, in a process known as “chromosomal translocation”. Examination of chromosomal breaks has helped to identify the genes that cause neurofibromatosis type 1, familial polyposis Coli, and Duchenne muscular dystrophy. At least 20 different chromosomes have been identified as containing chromosomal translocations in patients with autism. In each of these patients the rearrangements have usually involved one to three chromosomes. Given the unusual number of chromosomal rearrangements associated with autism it is possible that some of the genes disrupted by translocations cause autism. Most patients with autism do not have chromosomal abnormalities. However, the same genes that are disrupted in autistic patients with chromosomal breaks can cause autism in patients with normal chromosomes through mutations. Once these breakpoint genes are identified, autism patients with cytogenetically normal chromosomes can be studied to see if their set of “candidate genes” contain mutations. Mutations that produce abnormal protein function can be caused by very subtle molecular substitutions that do not visibly change chromosomal structure at the cytogenetic level. Genes altered in subtle ways like this can cause disease in patients with normal chromosomes. We have identified AUTS2, a candidate gene for autism in a pair of twins with a chromosomal translocation and autism. Further analysis of the chromosomal breakpoints in these twins and another autistic patient with a complex chromosomal rearrangement suggests that these rearrangements are caused by duplications of DNA segments resulting in genomic instability. The instability resulting from such duplications has been implicated to be the causative mechanism in Di George, Angelman, and Prader-Willi syndromes. It is of interest that a significant number of patients with these syndromes meet criteria for autism. The current focus of our research is 1) to determine if AUTS2 is involved in autism in patients without translocations 2) to identify additional candidate genes in autistic patients with chromosomal translocations, and 3) to determine if abnormal duplications of DNA contribute to autism. Identification of genes that cause autism will lead to an understanding of the biological basis of this disorder and development of better treatments.







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