Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes.
Details
Serval ID
serval:BIB_E1ED2C4D437A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes.
Journal
EMBO molecular medicine
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Publication state
Published
Issued date
12/2015
Volume
7
Number
12
Pages
1565-1579
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Fragile X syndrome (FXS) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene (FMR1). Up to 60% of affected males fulfill criteria for autism spectrum disorder (ASD), making FXS the most frequent monogenetic cause of syndromic ASD. It is unknown, however, whether normal variants (independent of mutations) in the fragile X gene family (FMR1, FXR1, FXR2) and in FMR2 modulate autistic features. Here, we report an accumulation model of 8 SNPs in these genes, associated with autistic traits in a discovery sample of male patients with schizophrenia (N = 692) and three independent replicate samples: patients with schizophrenia (N = 626), patients with other psychiatric diagnoses (N = 111) and a general population sample (N = 2005). For first mechanistic insight, we contrasted microRNA expression in peripheral blood mononuclear cells of selected extreme group subjects with high- versus low-risk constellation regarding the accumulation model. Thereby, the brain-expressed miR-181 species emerged as potential "umbrella regulator", with several seed matches across the fragile X gene family and FMR2. To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes.
Keywords
Autistic Disorder/genetics, Fragile X Mental Retardation Protein/genetics, Fragile X Syndrome/genetics, Fragile X Syndrome/physiopathology, Humans, Male, MicroRNAs/biosynthesis, Mutation, Polymorphism, Single Nucleotide, RNA-Binding Proteins/genetics, Schizophrenia/genetics, Schizophrenia/physiopathology
Pubmed
Open Access
Yes
Create date
06/03/2017 17:23
Last modification date
20/08/2019 16:05