The central nervous system patterning gene variants associated with clinical symptom severity of autism spectrum disorders
Journal
Journal of the Formosan Medical Association
Journal Volume
116
Journal Issue
10
Pages
755-764
Date Issued
2017
Author(s)
Abstract
Background/Purpose Central nervous system (CNS) patterning genes are recognized as candidate genes for autism spectrum disorders (ASDs) based on neuroimaging and neuropathological evidence. Several genes that regulate CNS development are shown to be associated with ASD. Our previous family-based association study also revealed that a specific haplotype of WNT2 (wingless-type MMTV integration site family member 2) gene was overtransmitted to probands with ASD. Whether the CNS patterning genes moderate the clinical phenotype of ASD is unclear. This study investigated the genetic associations of WNT2, engrailed 2 (EN2), and forkhead box P2 (FOXP2) with the clinical symptom severity. Methods The sample included 391 patients (males, 88.3%; mean age ± standard deviation, 9.5 ± 4.4 years) diagnosed with ASDs. Tag single nucleotide polymorphisms (SNPs) of EN2, WNT2, and FOXP2 were genotyped. The single-locus and multilocus markers were tested for association. Results We found that multilocus markers of WNT2 were associated with stereotyped behaviors whereas the markers of FOXP2 tended to be associated with social deficits. Moreover, an SNP of WNT2 showed a trend to be associated with less inattentive symptoms. Conclusion Our findings that WNT2 and FOXP2 may moderate the clinical phenotypes of ASD provide evidence to support the possible universal effect of WNT2 and FOXP2 on neurodevelopmental symptom dimensions. Such findings warrant further validation in other independent samples. Trial registration: Clinical trial registration identifier: NCT00494754 ? 2017
SDGs
Other Subjects
engrailed 2 protein; methylphenidate; protein; transcription factor FOXP2; unclassified drug; Wnt2 protein; forkhead transcription factor; FOXP2 protein, human; Wnt2 protein; WNT2 protein, human; Article; autism; central nervous system; child; controlled study; disease severity; DSM-IV; female; gene frequency; gene locus; genetic association; genetic variation; genotype; haplotype; human; intelligence quotient; major clinical study; male; phenotype; school child; single nucleotide polymorphism; stereotypy; treatment outcome; Wechsler intelligence scale for children; adolescent; autism; genetics; pathophysiology; preschool child; severity of illness index; Taiwan; Adolescent; Autism Spectrum Disorder; Child; Child, Preschool; Female; Forkhead Transcription Factors; Haplotypes; Humans; Male; Phenotype; Polymorphism, Single Nucleotide; Severity of Illness Index; Taiwan; Wnt2 Protein
Publisher
Elsevier B.V.
Type
journal article