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Role of Neuralized1 and RGS14 Genes With ASD Patients

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ClinicalTrials.gov Identifier: NCT04865198
Recruitment Status : Completed
First Posted : April 29, 2021
Last Update Posted : April 29, 2021
Sponsor:
Information provided by (Responsible Party):
Yusuf Ozkul, TC Erciyes University

Study Description
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Brief Summary:
Autism Spectrum Disorder (ASD) is a broad spectrum neurodevelopmental disease. Some individuals with ADS by high cognitive functions are diagnosed with High Functioning Autism (HFA). Learning difficulties and memory problems are detected in children with ASD. 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 ASD (N=20) and HFA (N=20), and healthy controls(N=20) 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).

Condition or disease Intervention/treatment
Autism Spectrum Disorder High-functioning Autism Healthy Diagnostic Test: Neurl1 gene expression Diagnostic Test: RGS14 gene expression

Detailed Description:

Autism Spectrum Disorders (ASD) is a complex and neuro-developmental disease starting in the early stages of life and is characterized by cognitive and behavioral disorders (Ansel et al., 2008). In addition, the definition of High Functioning Autism (HFA) is used for the individuals who are diagnosed with ASD with an Intelligence Quotient (IQ) of 70 and above with no mental disabilities (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).

It was shown in previous studies that individuals who are diagnosed with ASD have learning disabilities (Sullivan et al., 2019) and disorders in cognitive episodic memory, future planning, visual working memory (Goh and Peterson 2012). In some studies, it has been shown that NEURL1 gene increases learning and memory and RGS14 gene is suppressed them (Pavlopoulos et al., 2011; Lee et al., 2010). Considering this information, 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.

For RNA isolation, 2 ml of peripheral blood was taken from each subjects. RNA isolation was made in line with the recommended protocol by using the High Pure RNA Isolation Kit (Roche Diagnostic, Version 12, Germany) from the blood samples taken from the groups. The quality and quantity of the RNA was measured with nanodrop (Nanodrop 2000/Thermo Scientific, USA). Analyses were made in the RNAs by using the Transcriptor High Fidelity cDNA Synthesis Kit (Roche Diagnostics, GmbH, Mannheim). Since the amount of the target genes is less in the blood, pre-amplification was performed by applying Realtime Ready Assays (NEURL1, RGS14, ACTB genes primary and probes) and Multiplex PCR before Real Time PCR.

The expression of the NEURL1 and RGS14 genes were determined with the Semiquantitative Real-Time PCR Method by using the hybrid probe. The LightCycler®480 Real Time Ready Assay Master Probe Kit (Roche Diagnostics, GmbH, Mannheim) was used, and the analysis was made in Light Cycler in the study. 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 2-ΔΔCT method was applied for the relative quantification of the samples that were normalized with ACTB.

Statisticaly:

The fitness of the data to normal distribution was evaluated with Histogram, q-q graphics, and Shapiro-Wilk Test. Variance homogeneity was evaluated with the Levene Test. Inter-group comparisons were evaluated with the Pearson's Chi-Square analysis and Fisher's Exact Chi-Square Test for qualitative variables, and with Mann-Whitney U-Test, Kruskal-Wallis H-Test, and One-Way Variance Analysis for quantitative variables. Spearman's test was used for correlation analysis. The data were expressed as mean and standard deviation, or median with 25 and 75 percentages. The analysis of the data was made at R 3.1.1 (www.r-project.org). The P<0.05 level was taken as significant.

Study Design
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Study Type : Observational
Actual Enrollment : 60 participants
Observational Model: Other
Time Perspective: Cross-Sectional
Official Title: Relations of Neuralized1 and RGS14 Genes With Memory and Learning in Patients With Autism Spectrum Disorders
Actual Study Start Date : January 10, 2013
Actual Primary Completion Date : August 30, 2014
Actual Study Completion Date : August 30, 2014

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Patients with Autism Spectrum Disorder (ASD)
Patients diagnosed with ASD in a child psychiatry clinic.
 Diagnostic Test: Neurl1 gene expression
This observational case control study. The gene expression was examined.

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

Diagnostic Test: RGS14 gene expression
This observational case control study. The gene expression was examined.
Healty control
Healthy volunteers who are in the age range compatible with the patient groups.
 Diagnostic Test: Neurl1 gene expression
This observational case control study. The gene expression was examined.

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


Outcome Measures
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Primary Outcome Measures :
  1. NEURL1 gene expression levels [ Time Frame: Two months ]
    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.

  2. RGS14 gene expression levels [ Time Frame: Two months ]
    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.


Secondary Outcome Measures :
  1. Age [ Time Frame: an average of 1 year ]
    Age of subjects

  2. Gender [ Time Frame: an average of 1 year ]
    Gender (male/female) of subjects

  3. Intellectual disability (ID) [ Time Frame: an average of 1 year ]
    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.

  4. Consanguinity [ Time Frame: an average of 1 year ]
    Relationships of consanguinity between subjects were evaluated in terms of pathogenesis of the disease.

  5. Presence of Neurological Disease in Relatives [ Time Frame: an average of 1 year ]
    In the presence of a neurological disease in relatives, its relationship with the pathogenesis of the disease was evaluated.

  6. Corelation tests [ Time Frame: an average of 1 year" ]
    The relationships of the clinical and demographical findings in the study groups with the genes were evaluated statistically.


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.

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability 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
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04865198


Sponsors and Collaborators
TC Erciyes University
Investigators
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Principal Investigator: 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
Study Chair: Yusuf Özkul, Prof. Dr. TC Erciyes University
More Information
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Additional Information:

Publications of Results:

Other Publications:

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Responsible Party: Yusuf Ozkul, Professor, TC Erciyes University
ClinicalTrials.gov Identifier: NCT04865198    
Other Study ID Numbers: NEURL1RGS14
First Posted: April 29, 2021    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: The details and reports of the study will be shared after the article is published.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yusuf Ozkul, TC Erciyes University:
ASD
High Functioning Autism
NEURL1
RGS14
Gene expression
Additional relevant MeSH terms:
Layout table for MeSH terms
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders