Neuralized1 and RGS14 Genes

Healthy Clinical Trial

Official title:

Role of Neuralized1 and RGS14 Genes With ASD Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04865198
• Other study ID #: NEURL1RGS14
• Status: Completed
• Start date: January 10, 2013
• Est. completion date: August 30, 2014

Study information

• Verified date: July 2022
• Source: TC Erciyes University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Description:

ASD is a neurological disease starting in the early stages of life and is characterized by cognitive and behavioral disorders (Ansel et al., 2008;Alvares et al., 2020). It is considered that the etiology of ASD stems from genetic, epigenetic and environmental factors; however, it has not yet been definitively clarified(Ito et al., 2017). 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. Method: Patients with ASD (n=20) and HFA (n=20), and healthy controls (n=20) compatible with patient ages were included in this study. Clinical evaluations of the patients were made and classification was made in accordance with DSM-IV diagnostic criteria. High Pure RNA Isolation Kit (Roche Diagnostic, Version 12, Germany) was used for RNA isolation. cDNA synthesis was performed from these RNAs with the ranscriptor High Fidelity cDNA Synthesis Kit (Roche Diagnostics, GmbH, Mannheim). qRT-PCR was performed using the LightCycler®480 Real Time Ready Assay Master Probe Kit (Roche Diagnostics, GmbH, Mannheim).The incubation was made with the PCR device program for 10 minutes at 95oC for 45 cycles, for 10 sec at 95oC, and for 60 sec at 60oC. The Ct values were obtained from the Light Cycler 480 Software Program, and both genes were analyzed separately. The comparative CT method (2-ΔΔCT) was used to determine the relative quantification of target genes, normalized to a housekeeping gene (β-actin). Statisticaly: The results of the experiments were evaluated using R 3.1.1 (www.r-project.org). and Chi-Square Tests, Mann-Whitney U-Test, Kruskal-Wallis H-Tests. The P<0.05 level was taken as significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 30, 2014
• Est. primary completion date: August 30, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years to 16 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Healthy
• High-functioning Autism

Intervention

Diagnostic Test:
• Neurl1 gene expression
This observational case control study. The gene expression was examined.
• RGS14 gene expression
This observational case control study. The gene expression was examined.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
TC Erciyes University

References & 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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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). pii: ENEURO.0353-17.2018. doi: 10.1523/ENEURO.0353-17.2018. — View Citation

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. Review. — View Citation

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.201 — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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 hippoca — View Citation

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. — View Citation

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

O'Brien G, Pearson J. Autism and learning disability. Autism. 2004 Jun;8(2):125-40. Review. — View Citation

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/ — View Citation

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. Epub 2007 Jul 20. Review. — View Citation

Richter JD. Cytoplasmic polyadenylation in development and beyond. Microbiol Mol Biol Rev. 1999 Jun;63(2):446-56. Review. — View Citation

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. — View Citation

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 Ja — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NEURL1 gene expression levels	After RNA isolation from blood samples of the subjects, NEURL1 gene expression was studied by QPCR method. The 2-??CT method was applied for the relative quantification of the samples that were normalized with ACTB.	Two months
Primary	RGS14 gene expression levels	After RNA isolation from blood samples of the subjects, RGS14 gene expression was studied by QPCR method. The 2-??CT method was applied for the relative quantification of the samples that were normalized with ACTB.	Two months
Secondary	Age	Age of subjects	an average of 1 year
Secondary	Gender	Gender (male/female) of subjects	an average of 1 year
Secondary	Intellectual disability (ID)	Intellectual disability is when a person has certain limitations in cognitive functioning and skills, including communication, social and self-care skills.It was determined according to DSM-IV diagnostic criteria and clinical evaluation.	an average of 1 year
Secondary	Consanguinity	Relationships of consanguinity between subjects were evaluated in terms of pathogenesis of the disease.	an average of 1 year
Secondary	Presence of Neurological Disease in Relatives	In the presence of a neurological disease in relatives, its relationship with the pathogenesis of the disease was evaluated.	an average of 1 year
Secondary	Corelation tests	The relationships of the clinical and demographical findings in the study groups with the genes were evaluated statistically.	an average of 1 year"

External Links

•   American Psychiatric Association. Diagnostic and statistical manual of mental disorders
•   Centers for Disease Control and Prevention, Data and Statistics on Autism Spectrum Disorder