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.

最近，在一个常染色体隐性遗传模式下，在以色列发现了一个近亲家庭，其中三个孩子受到婴儿眼球震颤和中央凹发育不足的影响。纯合终止突变c.1861C> T; 芳烃受体中的Q621 ^*AHR）基因（AHR; 已确定MIM 600253与大家庭中的该疾病共隔离。AHR是第一个被鉴定为导致人类常染色体隐性遗传性小儿眼球震颤相关疾病的基因。这项研究的目的是描述这种新发现的与罕见病有关的人类遗传疾病的分子基础。AHR基因突变。番茄的基因和蛋白质表达水平AHR 然后选择 AHR分析了健康受试者和患者的白细胞培养物中的靶标。我们观察到在休息和AHR诱导的条件下CYP1A1，CYP1B1和TiPARP的mRNA和蛋白表达之间的显着差异。在患者和健康志愿者之间，诱导的白细胞中的CYP1A1酶活性也有显着差异。有趣的是，杂合受试者显示出与纯合患者相似的CYP1A1和TiPARP基因和蛋白质表达。相反，CYP1B1的诱导性和表达在杂合子和纯合子之间有所不同。杂合子和纯合患者之间基因和蛋白质表达的相似性和差异可以给我们提示眼球震颤病因可能涉及哪些代谢途径的提示。从而，