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

• Conditions: Mutation, Point
• Interventions: Diagnostic Test: Blood for protein activity

• Registration Number: NCT03566745
• Lead Sponsor: Hillel Yaffe Medical Center

Brief 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

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 Timeline

• Status Verified: 2018-06
• Study First Submitted: 2018-06-12
• Study First Submitted QC: 2018-06-12
• Last Update Submitted: 2018-06-12
• Study First Posted: 2018-06-25
• Last Update Posted: 2018-06-25
• Study Start: 2018-07-01
• Primary Completion: 2019-06-30
• Study Completion: 2019-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• patients with mutation in AhR gene

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Study group	Blood for protein activity	Patients with mutation in AhR gene - presumed low Blood for protein activity
Control	Blood for protein activity	Patients without mutation in AhR gene - presumed normal Blood for protein activity

Primary Outcome Measures

Name	Time	Method
Low protein activity	1 year	Low protein activity