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

NCT ID: NCT03566745

Last Updated: 2018-06-25

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 14 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2019-11-30

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.

Conditions

Mutation, Point

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Study group

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

Blood for protein activity

Intervention Type: DIAGNOSTIC_TEST

Blood for protein activity

Control

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

Blood for protein activity

Intervention Type: DIAGNOSTIC_TEST

Blood for protein activity

Interventions

Blood for protein activity

Blood for protein activity

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• patients with mutation in AhR gene

Exclusion Criteria

• None

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hillel Yaffe Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Muhammad Mahajnah

Head, Institute of pediatric neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Muhammad Mahajnah, MD PhD

Role: STUDY_CHAIR

Hillel Yaffe mediacl center

Central Contacts

Muhammad Mahajnah, MD PhD

Role: CONTACT

mohamedm@hy.health.gov.il

+972506246959

References

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.

Reference Type: BACKGROUND

PMID: 28851966 (View on PubMed)

Other Identifiers

0034-18-HYMC

Identifier Type: -

Identifier Source: org_study_id