Elucidating the Molecular and Biochemical Basis of the Human AhR-mutation Disease

Mutation, Point Clinical Trial

Official title:

Elucidating the Molecular and Biochemical Basis of the Human AhR-mutation Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03566745
• Other study ID #: 0034-18-HYMC
• Status: Not yet recruiting
• Start date: July 1, 2018
• Est. completion date: November 30, 2019

Study information

• Verified date: June 2018
• Source: Hillel Yaffe Medical Center
• Contact: Muhammad Mahajnah, MD PhD
• Phone: +972506246959
• Email: mohamedm[@]hy.health.gov.il
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In a previous study, we have identified a consanguineous family from Northern Israel with three children affected by idiopathic infantile nystagmus (IIN) and foveal hypoplasia, which follow an autosomal recessive mode of inheritance of AhR gene. in this study we will determine whether the disease phenotype is the consequence of a decrease in or absence of AHR-induced AHH activity

Description:

In a previous study, we have identified a consanguineous family from Northern Israel with three children affected by idiopathic infantile nystagmus (IIN) and foveal hypoplasia, which follow an autosomal recessive mode of inheritance of AhR gene. in this study we will:

1. To determine whether the disease phenotype is the consequence of a decrease in or absence of AHR-induced AHH activity. To this end, basal and ligand-mediated AHH enzyme activity will be compared in heterozygotic and homozygotic family members versus healthy volunteers.

2. To examine steady state protein levels of the AHR protein in cells of homo- and heterozygotic patients versus those of healthy volunteers. If no mutant protein is detected, we will determine the effect of the mutation on mRNA stability.

3. To analyze steady state levels of related partner proteins (such as ANRT) and proteins levels of transcriptional targets (AHH) in heterozygotic and homozygotic family members versus healthy volunteers.

4. To investigate the ability of the mutant allele to induce transcriptional activation in an engineered yeast test system. We will use a yeast strain engineered to contain human AHR and AHR nuclear translocator together with a reporter gene to investigate whether the mutation interferes with transcription activation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 14
• Est. completion date: November 30, 2019
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• patients with mutation in AhR gene

Exclusion Criteria:

Related Conditions & MeSH terms

• Mutation, Point

Intervention

Diagnostic Test:
• Blood for protein activity
Blood for protein activity

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hillel Yaffe Medical Center

References & Publications (1)

Juricek L, Carcaud J, Pelhaitre A, Riday TT, Chevallier A, Lanzini J, Auzeil N, Laprévote O, Dumont F, Jacques S, Letourneur F, Massaad C, Agulhon C, Barouki R, Beraneck M, Coumoul X. AhR-deficiency as a cause of demyelinating disease and inflammation. Sci Rep. 2017 Aug 29;7(1):9794. doi: 10.1038/s41598-017-09621-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Low protein activity	Low protein activity	1 year