Abstract:
Genome-wide scans have revealed a significant role for de novo copy number variants (CNVs) and Single Nucleotide variants (SNVs) in the genetic architecture of
schizophrenia. The present study attempts to parse schizophrenia based on the presence of such de novo mutations and attempts genotype–phenotype correlation.
We examined phenotypic variables across three broad categories: clinical presentation, premorbid function, disease course and functional outcome and compared
them in individuals with schizophrenia carrying either a de novo CNV, a de novo SNV, or no de novo mutation. Work skills were worst affected in patients carrying
de novo CNVs. More learning disabilities were found in subjects carrying de novo SNVs. Patients with either mutation had older parents at birth and worse
functional outcome as measured by SLOF scores. We found no relation between treatment resistance and the presence of de novo mutations. The combined
consideration of the functional outcome scores and early deviant behaviours was found to have higher predictive value for underlying genetic vulnerability. Due to
the rare nature of the de novo mutations the sample sizes studied here were small. Despite this, valuable phenotypic characteristics were identified in
schizophrenia patients carrying de novo mutations and studying larger samples will be of interest.
