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

Hillel Yaffe Medical Center

Status: Unknown

Conditions: Mutation, Point

Treatments: Diagnostic Test: Blood for protein activity

Study type: Observational

Funder types: Other

Identifiers

NCT03566745

0034-18-HYMC

Details and patient eligibility

About

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

Full 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.

Enrollment: 14 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• patients with mutation in AhR gene

Exclusion criteria

• None

Trial design

14 participants in 2 patient groups

Study group

Description:

Patients with mutation in AhR gene - presumed low Blood for protein activity

Treatment:

Diagnostic Test: Blood for protein activity

Control

Description:

Patients without mutation in AhR gene - presumed normal Blood for protein activity

Treatment:

Diagnostic Test: Blood for protein activity