NCT04865198

Brief Summary

Autism is a broad spectrum neurodevelopmental disease. Some individuals with ADS by high cognitive functions are diagnosed with High Functioning Autism (HFA). In some studies, it has been shown that NEURL1 gene increases learning and memory and RGS14 gene is suppressed them. We aimed to evaluate the differences between the expression levels of these genes between ASD, HFA and healthy controls and the role of these genes in the pathogenesis of ASD. Patients with 20 ASD and 20 HFA, and 20 healthy controls compatible with patient ages were included in this study. Expression of NEURL-1 and RGS14 genes was evaluated by quantitative Real Time PCR (qRT-PCR).

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Jan 2013

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 10, 2013

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 30, 2014

Completed
6.6 years until next milestone

First Submitted

Initial submission to the registry

April 20, 2021

Completed
9 days until next milestone

First Posted

Study publicly available on registry

April 29, 2021

Completed
Last Updated

July 26, 2022

Status Verified

July 1, 2022

Enrollment Period

1.6 years

First QC Date

April 20, 2021

Last Update Submit

July 22, 2022

Conditions

Autism Spectrum DisorderHigh-functioning AutismHealthy

Keywords

ASDHigh Functioning AutismNEURL1RGS14Gene expression

Outcome Measures

Primary Outcomes (2)

  • NEURL1 gene expression levels

    After RNA isolation from blood samples of the subjects, NEURL1 gene expression was studied by QPCR method. The 2-ΔΔCT method was applied for the relative quantification of the samples that were normalized with ACTB.

    Two months

  • RGS14 gene expression levels

    After RNA isolation from blood samples of the subjects, RGS14 gene expression was studied by QPCR method. The 2-ΔΔCT method was applied for the relative quantification of the samples that were normalized with ACTB.

    Two months

Secondary Outcomes (6)

  • Age

    an average of 1 year

  • Gender

    an average of 1 year

  • Intellectual disability (ID)

    an average of 1 year

  • Consanguinity

    an average of 1 year

  • Presence of Neurological Disease in Relatives

    an average of 1 year

  • +1 more secondary outcomes

Study Arms (3)

Patients with Autism Spectrum Disorder (ASD)

Patients diagnosed with ASD in a child psychiatry clinic.

Diagnostic Test: Neurl1 gene expressionDiagnostic Test: RGS14 gene expression

Patients with High Functioning Autism (HFA)

Patients diagnosed with ASD in a child psychiatry clinic and with an IQ above 70.

Diagnostic Test: Neurl1 gene expressionDiagnostic Test: RGS14 gene expression

Healty control

Healthy volunteers who are in the age range compatible with the patient groups.

Diagnostic Test: Neurl1 gene expressionDiagnostic Test: RGS14 gene expression

Interventions

Neurl1 gene expressionDIAGNOSTIC_TEST

This observational case control study. The gene expression was examined.

Healty controlPatients with Autism Spectrum Disorder (ASD)Patients with High Functioning Autism (HFA)
RGS14 gene expressionDIAGNOSTIC_TEST

This observational case control study. The gene expression was examined.

Healty controlPatients with Autism Spectrum Disorder (ASD)Patients with High Functioning Autism (HFA)

Eligibility Criteria

Age2 Years - 16 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)
Sampling MethodProbability Sample
Study Population

Group 1: Patients diagnosed with ASD in a child psychiatry clinic. Group 2: Patients diagnosed with HFA in a child psychiatry clinic. Group 3: Healty controls

You may qualify if:

  • Being diagnosed ASD or HFA patient,
  • Being between the ages of 2-16.

You may not qualify if:

  • To use medicine,
  • Have a other syndromic illness,
  • Being younger than 2 years old or over 16 years old.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (24)

  • Ansel A, Rosenzweig JP, Zisman PD, Melamed M, Gesundheit B. Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies. Front Neurosci. 2017 Jan 5;10:601. doi: 10.3389/fnins.2016.00601. eCollection 2016.

    PMID: 28105001BACKGROUND

  • Charman T, Baird G. Practitioner review: Diagnosis of autism spectrum disorder in 2- and 3-year-old children. J Child Psychol Psychiatry. 2002 Mar;43(3):289-305. doi: 10.1111/1469-7610.00022.

    PMID: 11944873BACKGROUND

  • Ito H, Morishita R, Nagata KI. Autism spectrum disorder-associated genes and the development of dentate granule cells. Med Mol Morphol. 2017 Sep;50(3):123-129. doi: 10.1007/s00795-017-0161-z. Epub 2017 May 22.

    PMID: 28534217BACKGROUND

  • Rao PA, Beidel DC, Murray MJ. Social skills interventions for children with Asperger's syndrome or high-functioning autism: a review and recommendations. J Autism Dev Disord. 2008 Feb;38(2):353-61. doi: 10.1007/s10803-007-0402-4. Epub 2007 Jul 20.

    PMID: 17641962BACKGROUND

  • Sener EF, Cikili Uytun M, Korkmaz Bayramov K, Zararsiz G, Oztop DB, Canatan H, Ozkul Y. The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders. Metab Brain Dis. 2016 Jun;31(3):613-9. doi: 10.1007/s11011-016-9795-0. Epub 2016 Jan 19.

    PMID: 26782176BACKGROUND

  • Misra V. The social brain network and autism. Ann Neurosci. 2014 Apr;21(2):69-73. doi: 10.5214/ans.0972.7531.210208.

    PMID: 25206065BACKGROUND

  • Sullivan JM, De Rubeis S, Schaefer A. Convergence of spectrums: neuronal gene network states in autism spectrum disorder. Curr Opin Neurobiol. 2019 Dec;59:102-111. doi: 10.1016/j.conb.2019.04.011. Epub 2019 Jun 18.

    PMID: 31220745BACKGROUND

  • O'Brien G, Pearson J. Autism and learning disability. Autism. 2004 Jun;8(2):125-40. doi: 10.1177/1362361304042718.

    PMID: 15165430BACKGROUND

  • Landsiedel J, Williams DM, Abbot-Smith K. A Meta-Analysis and Critical Review of Prospective Memory in Autism Spectrum Disorder. J Autism Dev Disord. 2017 Mar;47(3):646-666. doi: 10.1007/s10803-016-2987-y.

    PMID: 28116668BACKGROUND

  • Vellano CP, Lee SE, Dudek SM, Hepler JR. RGS14 at the interface of hippocampal signaling and synaptic plasticity. Trends Pharmacol Sci. 2011 Nov;32(11):666-74. doi: 10.1016/j.tips.2011.07.005. Epub 2011 Sep 8.

    PMID: 21906825BACKGROUND

  • Lamsa K, Lau P. Long-term plasticity of hippocampal interneurons during in vivo memory processes. Curr Opin Neurobiol. 2019 Feb;54:20-27. doi: 10.1016/j.conb.2018.08.006. Epub 2018 Sep 5.

    PMID: 30195105BACKGROUND

  • Zeithamova D, Schlichting ML, Preston AR. The hippocampus and inferential reasoning: building memories to navigate future decisions. Front Hum Neurosci. 2012 Mar 26;6:70. doi: 10.3389/fnhum.2012.00070. eCollection 2012.

    PMID: 22470333BACKGROUND

  • Besag FM. Epilepsy in patients with autism: links, risks and treatment challenges. Neuropsychiatr Dis Treat. 2017 Dec 18;14:1-10. doi: 10.2147/NDT.S120509. eCollection 2018.

    PMID: 29296085BACKGROUND

  • Richter JD. Cytoplasmic polyadenylation in development and beyond. Microbiol Mol Biol Rev. 1999 Jun;63(2):446-56. doi: 10.1128/MMBR.63.2.446-456.1999.

    PMID: 10357857BACKGROUND

  • Jacobs D, Steyaert J, Dierickx K, Hens K. Physician View and Experience of the Diagnosis of Autism Spectrum Disorder in Young Children. Front Psychiatry. 2019 May 28;10:372. doi: 10.3389/fpsyt.2019.00372. eCollection 2019.

    PMID: 31191373RESULT

  • Goh S, Peterson BS. Imaging evidence for disturbances in multiple learning and memory systems in persons with autism spectrum disorders. Dev Med Child Neurol. 2012 Mar;54(3):208-13. doi: 10.1111/j.1469-8749.2011.04153.x. Epub 2012 Jan 23.

    PMID: 22269006RESULT

  • Pavlopoulos E, Trifilieff P, Chevaleyre V, Fioriti L, Zairis S, Pagano A, Malleret G, Kandel ER. Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage. Cell. 2011 Dec 9;147(6):1369-83. doi: 10.1016/j.cell.2011.09.056.

    PMID: 22153079RESULT

  • Jaagura M, Taal K, Koppel I, Tuvikene J, Timmusk T, Tamme R. Rat NEURL1 3'UTR is alternatively spliced and targets mRNA to dendrites. Neurosci Lett. 2016 Dec 2;635:71-76. doi: 10.1016/j.neulet.2016.10.041. Epub 2016 Oct 22.

    PMID: 27780737RESULT

  • Taal K, Tuvikene J, Rullinkov G, Piirsoo M, Sepp M, Neuman T, Tamme R, Timmusk T. Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. Sci Rep. 2019 May 8;9(1):7104. doi: 10.1038/s41598-019-43069-x.

    PMID: 31068605RESULT

  • Lee SE, Simons SB, Heldt SA, Zhao M, Schroeder JP, Vellano CP, Cowan DP, Ramineni S, Yates CK, Feng Y, Smith Y, Sweatt JD, Weinshenker D, Ressler KJ, Dudek SM, Hepler JR. RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16994-8. doi: 10.1073/pnas.1005362107. Epub 2010 Sep 13.

    PMID: 20837545RESULT

  • Squires KE, Gerber KJ, Pare JF, Branch MR, Smith Y, Hepler JR. Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain. Brain Struct Funct. 2018 Jan;223(1):233-253. doi: 10.1007/s00429-017-1487-y. Epub 2017 Aug 3.

    PMID: 28776200RESULT

  • Martin KC, Casadio A, Zhu H, Yaping E, Rose JC, Chen M, Bailey CH, Kandel ER. Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage. Cell. 1997 Dec 26;91(7):927-38. doi: 10.1016/s0092-8674(00)80484-5.

    PMID: 9428516RESULT

  • Hosoda N, Funakoshi Y, Hirasawa M, Yamagishi R, Asano Y, Miyagawa R, Ogami K, Tsujimoto M, Hoshino S. Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase. EMBO J. 2011 Apr 6;30(7):1311-23. doi: 10.1038/emboj.2011.37. Epub 2011 Feb 18.

    PMID: 21336257RESULT

  • Evans PR, Parra-Bueno P, Smirnov MS, Lustberg DJ, Dudek SM, Hepler JR, Yasuda R. RGS14 Restricts Plasticity in Hippocampal CA2 by Limiting Postsynaptic Calcium Signaling. eNeuro. 2018 Jun 4;5(3):ENEURO.0353-17.2018. doi: 10.1523/ENEURO.0353-17.2018. eCollection 2018 May-Jun.

    PMID: 29911178RESULT

Related Links

Biospecimen

Retention: SAMPLES WITHOUT DNA

In this study, 2 ml of peripheral blood was taken from each subject. RNA was isolated from peripheral blood followed by cDNA synthesis. RNA and cDNA samples of the subjects were preserved.

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, PervasiveNeurodevelopmental DisordersMental Disorders

Study Officials

  • Hamiyet Eciroğlu, Phd. St.

    Alanya Alaaddin Keykubat University

    PRINCIPAL INVESTIGATOR

  • Elif F. Şener, Assoc. Prof.

    TC Erciyes University

    PRINCIPAL INVESTIGATOR

  • Didem B. Öztop, Assoc. Prof.

    Ankara University

    PRINCIPAL INVESTIGATOR

  • Sevgi Özmen, Assoc. Prof.

    TC Erciyes University

    PRINCIPAL INVESTIGATOR

  • Dilek Kaan, Phd.

    TC Erciyes University

    PRINCIPAL INVESTIGATOR

  • Yusuf Özkul, Prof. Dr.

    TC Erciyes University

    STUDY CHAIR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

April 20, 2021

First Posted

April 29, 2021

Study Start

January 10, 2013

Primary Completion

August 30, 2014

Study Completion

August 30, 2014

Last Updated

July 26, 2022

Record last verified: 2022-07