PDF(Pubmed)
Abstract：
An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.
摘要：
据估计，每10万人中就有1人出生时没有嗅觉，一种被称为先天性嗅觉缺失的疾病，大约三分之一的人患有非综合征，或孤立的先天性无嗅觉症（ICA）。尽管嗅觉对我们的生活质量有重大影响，ICA的根本原因在很大程度上仍然未知。在10个家族和141个ICA个体中使用全外显子组测序（WES），我们确定了162个罕见的候选名单，隔离，158个基因中的有害变异。我们证实了CNGA2的参与，CNGA2是先前涉及的ICA基因，是嗅觉转导途径的重要组成部分。此外，我们从家族基因候选列表中发现了SREK1IP1的功能缺失变异体，在另一个ICA非家庭队列中，5%的个体也观察到了这一点。虽然SREK1IP1以前没有与嗅觉相关，它在锌离子结合中的作用表明了对嗅觉信号的潜在影响。这项研究为ICA患者的遗传改变及其病因提供了更全面的了解，这可以改善诊断，预后,和治疗这种疾病，并导致更好地理解控制基本嗅觉功能的机制。
