Phenotypic features of patients with schizophrenia carrying de novo gene mutations: A pilot study

• Phenotypic variables are assessed across three categories: clinical presentation, premorbid function and disease course & functional outcome.
• An increase in learning disabilities are found in the de novo SNV group.
• The de novo SNV and -CNV group had older parents and poorer functional outcome.
• The combined use of the SLOF and the early deviant behaviour checklist evidently has higher predictive value for underlying genetic vulnerability.

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.