title: Phenotypic features of patients with schizophrenia carrying de novo gene mutations: a pilot study.
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.
authors.affiliation: Department of Psychiatry, University of Pretoria, Weskoppies Hospital, Private Bag X113, Pretoria 0001, South Africa.
authors.forename: P J
authors.initials: PJ
authors.lastname: Malherbe
authors.affiliation: Department of Psychiatry, University of Pretoria, Weskoppies Hospital, Private Bag X113, Pretoria 0001, South Africa.
authors.forename: J L
authors.initials: JL
authors.lastname: Roos
authors.affiliation: Department of Statistics, University of Pretoria, Pretoria, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Ehlers
authors.affiliation: Department of Psychiatry, Columbia University, New York, USA; Extraordinary Professor, University of Pretoria, Pretoria, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Karayiorgou
authors.affiliation: Department of Psychiatry, University of Pretoria, Weskoppies Hospital, Private Bag X113, Pretoria 0001, South Africa.
authors.forename: J L
authors.initials: JL
authors.lastname: Roos
mesh_terms: D000328:Adult; D017668:Age of Onset; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007859:Learning Disabilities / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D013223:Statistics as Topic
keywords: Copy number variant; Early deviance; Functional outcome; Paternal age; Rare mutation; Single nucleotide polymorphism