The 22q11.2 microdeletion: Fifteen years of insights into the genetic and neural complexity of psychiatric disorders

International Journal of Developmental Neuroscience - Tập 29 Số 3 - Trang 259-281 - 2011
Liam Drew1, Gregg W. Crabtree1, Sander Markx2, Kimberly L. Stark1,2, Florence Chaverneff1, Bin Xu1,2, Jun Mukai1, Karine Fénelon1, Pei‐Ken Hsu1,3, Joseph A. Gogos4,1, Maria Karayiorgou2,5
1Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
3Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, New York, NY 10032 USA
4Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
5New York State Psychiatric Institute, New York, NY, 10032 USA

Tóm tắt

Abstract

Over the last fifteen years it has become established that 22q11.2 deletion syndrome (22q11DS) is a true genetic risk factor for schizophrenia. Carriers of deletions in chromosome 22q11.2 develop schizophrenia at rate of 25–30% and such deletions account for as many as 1–2% of cases of sporadic schizophrenia in the general population. Access to a relatively homogeneous population of individuals that suffer from schizophrenia as the result of a shared etiological factor and the potential to generate etiologically valid mouse models provides an immense opportunity to better understand the pathobiology of this disease. In this review we survey the clinical literature associated with the 22q11.2 microdeletions with a focus on neuroanatomical changes. Then, we highlight results from work modeling this structural mutation in animals. The key biological pathways disrupted by the mutation are discussed and how these changes impact the structure and function of neural circuits is described.

Từ khóa


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