Gregory Costain, et al., Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays, Human Molecular Genetics, 2013
Using high-resolution genome-wide microarrays and rigorous methods, we investigated rare CNVs in a prospectively recruited community-based cohort of 459 unrelated adults with schizophrenia and estimated the minimum prevalence of clinically significant CNVs that would be detectable on a clinical microarray.
There were 16 CNVs considered clinically significant at eight loci. All were very rare, including six CNVs at four loci novel to schizophrenia: 2q13, 3q13.31, 5p15.33-p15.32 and 10q11.22-q11.23.
The results of this study indicate that ~1 in 13 unrelated patients with schizophrenia may harbor a clinically significant large rare structural variant that would be detectable using methods available in most clinical laboratories.
Our data also suggest that most individuals with schizophrenia who have large rare CNVs would not have obvious developmental (syndromal) features, with the exception of some with large exotic losses where phenotypes tend to be more complex, as in 22q11.2 deletions. Thus, to discover most of the clinically significant variants identified in this study a genome-wide microarray would be necessary.