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Study Shows a Link Between Schizophrenia & Genetic Mutations
Date:7/20/2009

LOS ANGELES, July 20 /PRNewswire/ -- A link between schizophrenia and ultra-rare variants in microRNA genes on the X-chromosome has been identified. Mutations in a subset of these regulatory RNA genes may strongly predispose to schizophrenia. The recently published study in PLoS ONE by the laboratories of Steve S. Sommer, MD, PhD and John J. Rossi, PhD reports the first association of microRNA dysfunction with schizophrenia. This breakthrough may have preventive or therapeutic implications.

Schizophrenia is a common and devastating brain disease, often presenting in the teens or twenties and affecting about 1% of the population. As affected individuals are typically handicapped for many decades, it is one of the costliest of diseases, roughly comparable with the aggregate cost of a serious cancer. Schizophrenia affects people of all races, ethnic groups, and socioeconomic status, including the economics professor with mild schizophrenia described in the movie "A Beautiful Mind". Some of the homeless population are affected with schizophrenia, as illustrated by the recent movie "The Soloist".

MicroRNAs (miRNA) are a large family of small, non-coding RNAs that down-regulate the expression of a variety of genes and are scattered over the genome. Components required for miRNA processing and/or function have been implicated in X-linked mental retardation, neurological diseases and cancer, suggesting wide ranging involvement of miRNAs in disease.

In this study, the sequences of 59 miRNA genes on the X-chromosome were determined in 193 men with schizophrenia and 191 without the disease. Men were chosen because they are much more commonly affected by mutations in genes on the X-chromosome. Eight ultra-rare variants in eight distinct miRNA genes were detected in 4% of the men with schizophrenia while none were detected in normal men. While 4% may seem to be a small percentage, it is actually a very substantial and significant finding since schizophrenia is believed to be associated with a variety of causes and a particular cause that may be responsible for 4% of the disease would be quite significant. Biochemical tests of the ultra-rare variants demonstrated alterations in miRNA function or expression levels.

The overwhelming majority of the miRNAs are NOT on the X-chromosome, so it is possible that mutations in the miRNA genes can predispose to 20% or more of all schizophrenia.

"While confirmation is required", says Dr Sommer, "this study suggests that microRNA gene mutations can contribute to schizophrenia. If correct, it offers early diagnosis with the promise of subsequent therapy to delay or perhaps even prevent schizophrenia in the subset of patients with miRNA deficiencies".

Says Dr. Rossi, "I am excited by the prospect of using micro RNAs as diagnostic markers for mental illness. It may be feasible to treat schizophrenia by restoring expression of normal microRNAs in the central nervous system with current technologies".

About MEDomics

MEDomics is a molecular diagnostic laboratory founded in 2008 by Steve S. Sommer, MD, PhD, with the mission of providing Mutation Expert-based Diagnosis ("MED") to support the physician in delivering personalized medicine based on analysis of the patient's genome ("omics"). The mutation experts at MEDomics provide unparalleled quality interpretation to aid the practicing physician.

Dr. Sommer is a Founding Fellow of the American College of Medical Genetics with 25 years experience in Clinical Molecular Diagnosis and 300(+ )scientific publications and patents. During the past few years, his neuropsychiatric genetics team helped to define the first genes for which high risk mutations can strongly predispose to schizophrenia or autism. His personalized cancer genetics research and clinical team, including Kelly Gonzalez and Bill Scaringe, discovered mutation showers. Mutation showers may occasionally cause cancer in an instant. Carolyn Buzin, PhD, Kelly Gonzalez MS, CGC, and Bill Scaringe, MS are currently Senior Scientist, Co-Director of Genetic Counseling & Education, and Director of Bioinformatics at MEDomics, respectively.

The laboratory work was performed in the Sommer and Rossi Labs at City of Hope Beckman Research Institute in Duarte, CA and the analysis was completed at MEDomics, LLC in neighboring Azusa. Since January, Dr Sommer has devoted full time effort to MEDomics.

MEDomics staff involved in the research study includes Steve Sommer, MD, PhD, and Carolyn Buzin, PhD. City of Hope researchers previously in Dr. Sommer's laboratory include lead author Jinong Feng, MD, Jin Yan, PhD, Wenyan Li, and Katie Noltner. Other City of Hope researchers include John Rossi, PhD, Guihua Sun, and Jeffrey Longmate, PhD.

Contact: Gary Grasso, 1-626-793-8964, doctorspr@yahoo.com


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