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

PSYCHIATRY RESEARCH

卷:225

Article

Malherbe, P. J.¹  Roos, J. L., Jr.¹  Ehlers, R.²  Karayiorgou, M.^3,4  Roos, J. L.¹ 

[1] Univ Pretoria, Weskoppies Hosp, Dept Psychiat, ZA-0001 Pretoria, South Africa

[2] Univ Pretoria, Dept Stat, ZA-0002 Pretoria, South Africa

[3] Columbia Univ, Dept Psychiat, New York, NY USA

[4] Univ Pretoria, ZA-0002 Pretoria, South Africa

关键词: Copy number variant;    Single nucleotide polymorphism;    Paternal age;    Rare mutation;    Early deviance;    Functional outcome;   

DOI  :  10.1016/j.psychres.2014.10.024

来源: Elsevier

【 摘 要 】

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 nova 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 nova CNVs. More learning disabilities were found in subjects carrying de nova SNVs. Patients with either mutation had older parents at birth and worse functional outcome as measured by SLOE 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 (C) 2014 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free