Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances.
Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances.
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DOI：
10.3389/fped.2017.00244
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发表时间：
2017
影响因子：
2.6
通讯作者：
Johnson CA
中科院分区：
文献类型：
--
作者：
Hartill V;Szymanska K;Sharif SM;Wheway G;Johnson CA
Meckel-Gruber综合征（MKS）是一种致死性常染色体隐性遗传先天性异常综合征，由编码蛋白质的基因突变引起，这些蛋白质是初级纤毛的结构或功能组分。由纤毛基因突变引起的疾病统称为纤毛病，MKS是这组疾病中最严重的疾病。初级纤毛是一种微管细胞器，从脊椎动物细胞的顶端表面伸出。它作为一个“天线”，接收和转导化学感觉和机械感觉信号，但也调节不同的信号通路，如Wnt和Shh，在胚胎发育过程中具有重要作用。大多数MKS蛋白定位于称为过渡区（TZ）的独特纤毛隔室，其调节货物蛋白或脂质的运输。在这篇综述中，我们提供了一个最新的总结MKS的临床特征，分子遗传学和临床诊断。MKS具有高度可变的表型，极端的遗传异质性，并显示与其他相关的纤毛病如Joubert综合征的等位性，对诊断提出了重大挑战。遗传技术的最新进展，随着多基因面板的广泛使用，分子检测，显着改善了诊断，遗传咨询和MKS家庭的临床管理。这些包括一些有限的基因型-表型相关性的描述。我们讨论最近的见解MKS疾病的分子基础，因为一些相关的纤毛蛋白的功能，现在已经确定。一种常见的分子病因似乎是睫状体TZ结构和功能的破坏，影响基本的发育信号传导和第二信使的调节。
Meckel–Gruber syndrome (MKS) is a lethal autosomal recessive congenital anomaly syndrome caused by mutations in genes encoding proteins that are structural or functional components of the primary cilium. Conditions that are caused by mutations in ciliary genes are collectively termed the ciliopathies, and MKS represents the most severe condition in this group of disorders. The primary cilium is a microtubule-based organelle, projecting from the apical surface of vertebrate cells. It acts as an “antenna” that receives and transduces chemosensory and mechanosensory signals, but also regulates diverse signaling pathways, such as Wnt and Shh, that have important roles during embryonic development. Most MKS proteins localize to a distinct ciliary compartment called the transition zone (TZ) that regulates the trafficking of cargo proteins or lipids. In this review, we provide an up-to-date summary of MKS clinical features, molecular genetics, and clinical diagnosis. MKS has a highly variable phenotype, extreme genetic heterogeneity, and displays allelism with other related ciliopathies such as Joubert syndrome, presenting significant challenges to diagnosis. Recent advances in genetic technology, with the widespread use of multi-gene panels for molecular testing, have significantly improved diagnosis, genetic counseling, and the clinical management of MKS families. These include the description of some limited genotype–phenotype correlations. We discuss recent insights into the molecular basis of disease in MKS, since the functions of some of the relevant ciliary proteins have now been determined. A common molecular etiology appears to be disruption of ciliary TZ structure and function, affecting essential developmental signaling and the regulation of secondary messengers.
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影响因子：
21.3
作者：
Chih, Ben;Liu, Peter;Peterson, Andrew S.
通讯作者：
Peterson, Andrew S.
影响因子：
9.8
作者：
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影响因子：
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通讯作者：
Valente, Enza Maria
影响因子：
4
作者：
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通讯作者：
Glass IA
影响因子：
9.8
作者：
Baala, Lekbir;Romano, Stephane;Attie-Bitach, Tania
通讯作者：
Attie-Bitach, Tania