Gene and Protein Expression in Subjects With a Nystagmus-Associated AHR Mutation

Natalia Borovok*, Celeste Weiss, Rajech Sharkia, Michal Reichenstein, Bernd Wissinger, Abdussalam Azem, Muhammad Mahajnah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Recently, a consanguineous family was identified in Israel with three children affected by Infantile Nystagmus and Foveal Hypoplasia, following an autosomal recessive mode of inheritance. A homozygous stop mutation c.1861C > T; p.Q621 in the aryl hydrocarbon receptor (AHR) gene (AHR; MIM 600253) was identified that co-segregated with the disease in the larger family. AHR is the first gene to be identified causing an autosomal recessive Infantile Nystagmus-related disease in humans. The goal of this study is to delineate the molecular basis of this newly discovered human genetic disorder associated with a rare AHR gene mutation. The gene and protein expression levels of AHR and selected AHR targets from leukocyte cultures of healthy subjects and the patients were analyzed. We observed significant variation between mRNA and protein expression of CYP1A1, CYP1B1, and TiPARP under rest and AHR-induced conditions. The CYP1A1 enzymatic activity in induced leukocytes also differs significantly between the patients and healthy volunteers. Intriguingly, the heterozygous subjects demonstrate CYP1A1 and TiPARP gene and protein expression similar to homozygous patients. In contrast, CYP1B1 inducibility and expression vary between hetero- and homozygous subjects. Similarity and differences in gene and protein expression between heterozygotes and homozygous patients can give us a hint as to which metabolic pathway/s might be involved in the Nystagmus etiology. Thus, we have a unique human model for AHR deficiency that will allow us the opportunity to study the biochemical basis of this rare human mutation, as well as the involvement of AHR in other physiological processes.

Original languageEnglish
Article number582796
JournalFrontiers in Genetics
StatePublished - 24 Sep 2020


FundersFunder number
Triangle Research and Development Center
Tel Aviv University30003072000


    • aryl hydrocarbon receptor
    • CYP1A1
    • CYP1B1
    • gene expression
    • human mutation
    • infantile nystagmus
    • protein expression
    • TiPARP


    Dive into the research topics of 'Gene and Protein Expression in Subjects With a Nystagmus-Associated AHR Mutation'. Together they form a unique fingerprint.

    Cite this