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

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

Study Overview

• Status: Unknown
• Conditions: Mutation, Point
• Intervention / Treatment: Diagnostic test: Blood for protein activity

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 14

Contacts and Locations

• Study Contact: Name: Muhammad Mahajnah, MD PhD; Phone Number: +972506246959; Email: mohamedm@hy.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Everyone

Description

Inclusion Criteria:

• patients with mutation in AhR gene

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Patients with mutation in AhR gene - presumed low Blood for protein activity	Diagnostic test: Blood for protein activity; Blood for protein activity
Control; Patients without mutation in AhR gene - presumed normal Blood for protein activity	Diagnostic test: Blood for protein activity; Blood for protein activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low protein activity	Low protein activity	1 year

Collaborators and Investigators

• Sponsor: Hillel Yaffe Medical Center
• Investigators: Study Chair: Muhammad Mahajnah, MD PhD, Hillel Yaffe mediacl center

Publications and helpful links

General Publications

• Juricek L, Carcaud J, Pelhaitre A, Riday TT, Chevallier A, Lanzini J, Auzeil N, Laprevote 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2018
• Primary Completion (Anticipated): June 30, 2019
• Study Completion (Anticipated): November 30, 2019

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: June 12, 2018
• First Posted (Actual): June 25, 2018

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 0034-18-HYMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No