Genetic profiles may predict future psychiatric diagnoses for patients with common deletion syndrome

Results of a recent study suggest the possibility that in the future, genetic profiling may be used to identify whether children with 22q11.2 Microdeletion Syndrome (22q11.2DS; Velocardiofacial/DiGeorge syndrome) are at risk for developing autism spectrum disorder (ASD) or psychosis.

As reported in PLoS One, the research identified a relationship between variability in the pattern of genome wide gene expression and behavioral expressions of 22q11DS.

“Early in life, the potential medical complications are the most salient issue for children with 22q11DS. However, psychiatric illnesses, particularly psychosis and ASD, are very common and becomes the major source of lifetime morbidity among patients with 22q11DS,” said Carrie Bearden, PhD, senior author and professor, department of psychiatry & behavioral biosciences and psychology, University of California Los Angeles.

“Substantial evidence that early intervention may improve outcomes for people with these psychiatric diagnoses speaks to the potential value of a predictive biomarker.”

Augmenting interest in this topic are recent data showing that 22q11DS is even more common than previously thought.

“New information indicates that the prevalence of 22q11DS may be as high as that of Down syndrome [Grati FR, et al. Prenat Diagn. 2015;35(8):801-9], and there are now groups advocating for 22q11DS to be included in the standard newborn genetic disorders screening panel,” Dr. Bearden said.

In their research, Dr. Bearden and colleagues performed integrated genomic analyses of blood specimens from 46 patients with 22q11DS and unaffected controls to identify genes related to the psychosis and ASD phenotypes. The 22q11DS population had a mean (±SD) age of 17.3 (11.9) years, and included 6 individuals diagnosed with a psychotic disorder (13%), 16 diagnosed with ASD (40%), and 3 with comorbid psychosis and ASD (6.5%).

Not only did the analyses identify distinct differences in the gene expression profiles between the psychosis and ASD patient subgroups, but there was significant overlap comparing their gene expression profiles with published datasets based on analyses of blood and brain tissue from individuals with idiopathic psychosis and ASD, respectively.

The researchers also performed weighted gene co-expression network analysis (WGCNA) to investigate biological pathways related to psychosis and ASD. WGCNA is a cutting edge technique developed by UCLA bioinformatician Steve Horvath, PhD, ScD, that allows identification of groups of functionally related genes whose expression patterns are highly correlated. Thus, it provides information that can improve understanding of functional disease mechanisms..

Dr. Bearden and coauthors noted that the findings from their research must be interpreted cautiously. Although the study is the largest to date of genome-wide gene expression in phenotypically well-characterized patients with 22q11DS, it included a relatively small number of individuals with psychosis. In addition, there were young children in the sample who may develop changing gene expression patterns over time as well as psychosis.

Finally, CNS tissue would have been the ideal specimen for the analyses.

“However, the findings support the feasibility of using blood as a surrogate for genomic analyses for future studies of mutational brain disorders. This is important given the feasibility of obtaining blood samples versus other kinds of tissue,” Dr. Bearden said.