The Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies.

IF 7.7 2区 生物学 Q1 GENETICS & HEREDITY
Julie C Van De Weghe, Arianna Gomez, Dan Doherty
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引用次数: 12

Abstract

The Joubert syndrome (JS), Meckel syndrome (MKS), and nephronophthisis (NPH) ciliopathy spectrum could be the poster child for advances and challenges in Mendelian human genetics over the past half century. Progress in understanding these conditions illustrates many core concepts of human genetics. The JS phenotype alone is caused by pathogenic variants in more than 40 genes; remarkably, all of the associated proteins function in and around the primary cilium. Primary cilia are near-ubiquitous, microtubule-based organelles that play crucial roles in development and homeostasis. Protruding from the cell, these cellular antennae sense diverse signals and mediate Hedgehog and other critical signaling pathways. Ciliary dysfunction causes many human conditions termed ciliopathies, which range from multiple congenital malformations to adult-onset single-organ failure. Research on the genetics of the JS-MKS-NPH spectrum has spurred extensive functional work exploring the broadly important role of primary cilia in health and disease. This functional work promises to illuminate the mechanisms underlying JS-MKS-NPH in humans, identify therapeutic targets across genetic causes, and generate future precision treatments.

纤毛病的joubert - meckel -肾病谱。
Joubert综合征(JS)、Meckel综合征(MKS)和肾盂肾炎(NPH)纤毛病谱系可能是过去半个世纪孟德尔人类遗传学进步和挑战的典型代表。了解这些情况的进展说明了人类遗传学的许多核心概念。单独的JS表型是由40多个基因的致病变异引起的;值得注意的是,所有相关蛋白都在初级纤毛内部和周围起作用。初级纤毛是几乎无处不在的微管细胞器,在发育和体内平衡中起着至关重要的作用。这些细胞触角从细胞中伸出,感知多种信号并介导Hedgehog和其他关键信号通路。纤毛功能障碍引起许多被称为纤毛病的人类疾病,其范围从多种先天性畸形到成人发病的单器官衰竭。对JS-MKS-NPH谱的遗传学研究促进了广泛的功能性工作,探索初级纤毛在健康和疾病中的广泛重要作用。这项功能性工作有望阐明人类JS-MKS-NPH的潜在机制,确定跨遗传原因的治疗靶点,并产生未来的精确治疗方法。
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来源期刊
CiteScore
14.90
自引率
1.10%
发文量
29
期刊介绍: Since its inception in 2000, the Annual Review of Genomics and Human Genetics has been dedicated to showcasing significant developments in genomics as they pertain to human genetics and the human genome. The journal emphasizes genomic technology, genome structure and function, genetic modification, human variation and population genetics, human evolution, and various aspects of human genetic diseases, including individualized medicine.
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