更新于：2024-11-01

Agenesis of Cerebellar Vermis

蚓部发育不全

更新于：2024-11-01

基本信息

别名

Agenesis of Cerebellar Vermis、Agenesis of cerebellar vermis、CEREBELLOOCULORENAL SYNDROME 1

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简介

A rare genetic syndrome characterized by the hypoplasia or absence of the cerebellar vermis. Signs and symptoms include rapid breathing (hyperpnea), sleep apnea, abnormal eye movements, mental retardation, and ataxia.

关联

项与蚓部发育不全相关的临床试验

NCT04874909 / RecruitingN/AIIT

Classification and Functional Stratification of the Patients With Ciliopathy and Identification of Biomarkers to Improve Their Prognosis

The purpose of the C'IL-LICO RICM study is to develop innovative and transformative diagnostic and prognostic for patients suffering from ciliopathies leading to renal failure.
The objectives is to decipher disease mechanisms and highlight signaling pathways altered in at-risk to develop renal failure patient groups and to produce a prognostic biomarker-based kit to predict the evolution of ciliopathy patients towards renal impairment.

开始日期2021-11-08

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

ChiCTR2100048366 / Suspended临床1期IIT

Complete transcriptome sequencing of Joubert syndrome

开始日期2021-07-01

申办/合作机构-

ChiCTR2100042216 / Recruiting早期临床1期IIT

Evaluation of ultrasonographic quantitative threshold in fetuses with vermian hypoplasia

开始日期2020-01-01

申办/合作机构-

100 项与蚓部发育不全相关的临床结果

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100 项与蚓部发育不全相关的转化医学

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0 项与蚓部发育不全相关的专利（医药）

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1,342

项与蚓部发育不全相关的文献（医药）

2025-01-01·Human Genetics and Genomics Advances

Togaram1 is expressed in the neural tube and its absence causes neural tube closure defects

Article

作者: Ninnemann, Olaf ; Hu, Hao ; Kaindl, Angela M ; Weng, Kai ; Kaindl, Angela M. ; Kraemer, Nadine ; Mani, Shyamala ; Reid, Joshua ; Schneider, Joanna ; Li, Na ; Hildebrand, Michael ; Wang, Yanyan

Neural tube closure defect pathomechanisms in human embryonic development are poorly understood. Here we identified spina bifida patients expressing novel variants of the TOGARAM gene family. TOGARAM1 has been associated with the ciliopathy Joubert syndrome, but its connection to spina bifida and role in neural development is unknown. We show that Togaram1 is expressed in the neural tube and Togaram1 knockout mice have abnormal cilia, reduced sonic hedgehog (Shh) signaling, abnormal neural tube patterning, and display neural tube closure defects. Neural stem cells from Togaram1 knockout embryos showed reduced cilia and defects in Shh signaling. Overexpression in IMCD3 and HEK293 cells of TOGARAM1 carrying the variant found in the spina bifida patient resulted in cilia defect along with reduced pericentriolar material one (PCM1), a critical constituent of centriolar satellites involved in transporting proteins toward the centrosome and primary cilia. Our results demonstrate the role of TOGARAM1 in regulating Shh signaling during early neural development that is critical for neural tube closure and elucidates potential mechanisms whereby the ciliopathy-associated gene TOGARAM1 gives rise to spina bifida aperta in humans.

2024-11-01·Pediatric Neurology

Developmental, Cognitive, Ocular Motor, and Neuroimaging Findings Related to SUFU Haploinsufficiency: Unraveling Subtle and Highly Variable Phenotypes

Article

作者: Kepa, Sylvia ; Grisold, Anna ; Laccone, Franco ; Schmook, Maria T. ; Schmidt, Wolfgang M. ; Krenn, Martin ; Schmidt, Wolfgang M ; Wiest, Gerald ; Pal-Handl, Katharina ; Lilja, Stephanie ; Schmook, Maria T ; Boltshauser, Eugen ; Pogledic, Ivana ; Silvaieh, Sara ; Siegert, Sandy

BACKGROUNDBiallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency.METHODSNine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing.RESULTSWe identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals.CONCLUSIONSOur data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time.

2024-10-05·Korean Journal of Ophthalmology

Coats-like Exudative Retinopathy in a Patient with Joubert Syndrome with CEP290 Mutation: A Case Report

Article

作者: Kim, Sang Jin ; Hwang, Sungsoon ; Goh, Yong Hyu

项与蚓部发育不全相关的新闻（医药）

2022-09-26

·生物谷

JCB：天津科技大学樊振川团队揭示一种全新的巴德-毕得氏综合症可能致病机制

不同于其他业已发现的ARL类纤毛小G蛋白，研究发现ARL3只在GDP结合状态下才能附着于细胞质膜，并以扩散的方式进入纤毛并富集于靠近纤毛TZ上部的部分。真核细胞纤毛（cilia）是由外披纤毛膜（特异化的细胞膜）的微管轴突组成的一类细胞器。纤毛作为真核细胞信号天线，赋予细胞感受外界刺激（如光、声、味、机械力和各类化学分子如激素和神经介质等）并将这些胞外信号传导到胞内进行应答的能力。近年来的研究已经充分表明，之前认为定位于细胞膜的许多重要信号分子包括G蛋白偶联受体、离子通道以及其他类型的信号蛋白均特异性定位于纤毛膜，这是决定纤毛作为信号天线的分子基础。目前已知这些跨纤毛膜或纤毛膜内膜附着的纤毛信号分子通过与分子动力蛋白驱动的鞭毛内运输火车（intraflagellar transport（IFT）train）进行偶联，从而使得这些个重要纤毛信号分子得以沿着纤毛微管轴丝在细胞膜和纤毛膜之间维持一种动态平衡。比如说Hedgehog信号通路受体Smo等在纤毛膜和细胞膜之间的动态循环过程当中，由多蛋白组分组成的蛋白复合物BBSome在Smo和反向IFT火车之间充当连接体，其功能就是把Smo偶联到反向IFT火车从而使其得以以IFT的方式输出纤毛。因此，导致BBSome组分缺失、组装缺陷或纤毛稳态失衡的基因突变均可使得Smo在纤毛膜内异常积累，从而阻断了hedgehog信号传导，最终引发巴德-毕德氏综合症（Bardet-Biedl syndrome，BBS）。到目前为止，多达20多个基因包括纤毛小G蛋白ARL3基因的突变均可导致一种称之为朱伯特综合征（Joubert syndrome，JBTS）的纤毛病。有趣的是，BBS和JBTS具有许多共有的临床病症包括视网膜褪变、雄性不育、肝囊肿、肾囊肿、多趾以及内分泌失调引发的代谢病如肥胖和糖尿病等。JBTS有别于BBS的地方在于其可导致脑干畸形引起的运动技能丧失和认知能力低下等更严重的临床症状。作为小G蛋白Ras超家族的Arf亚家族成员，ARL3在纤毛内可以PDE6D和UNC119A/B作为其效应子（effector）。PDE6D和UNC119A/B在胞质中充当载体蛋白以结合不同类的脂化信号蛋白如INPP5E、NPHP3和视紫红质激酶等并将他们精确定位于纤毛过渡区（transition zone，TZ），活化的ARL3GTP在与这些脂化信号蛋白货物结合位点不同的变构位点与其载体蛋白效应物结合，诱导载体蛋白发生构象变化，从而释放这些脂化信号蛋白使之与纤毛膜结合以行使正常功能。目前一般认为ARL3突变破坏了这一ARL3介导的纤毛信号蛋白纤毛输入途径而导致了JBTS的发生。然而，ARL3突变引发BBS临床症状的致病机理至今还没有被阐明。部分BBSome在纤毛TZ上方与IFT分离并扩散穿越纤毛TZ以输出纤毛示意图 2022年9月21日，天津科技大学樊振川课题组在 Journal of Cell Biology 期刊在线发表了题为：ARL3 mediates BBSome ciliary turnover by promoting its outward movement across the transition zone 的研究论文。该研究利用经典模式生物莱茵衣藻，通过分子，细胞，遗传，生化和活细胞成像的方法，发现ARL3利用BBSome作为其纤毛内效应子，通过招募BBSome穿越纤毛TZ输出纤毛这一机制控制纤毛信号分子磷酸酯酶D（PLD）在纤毛内的动态平衡。反映到人类细胞，ARL3很有可能是通过这一ARL3介导的外向BBSome纤毛TZ扩散途径来维持hedgehog信号通路分子在纤毛内的动态平衡。正因如此，某些ARL3突变既可破坏ARL3介导的纤毛信号蛋白纤毛输入导致JBTS，又可同时影响ARL3介导的依赖于BBSome的hedgehog信号分子纤毛输出从而引发BBS。这一发现可以帮助我们完善临床上针对BBS和JBTS致病基因的基因分型。不同于其他业已发现的ARL类纤毛小G蛋白，研究发现ARL3只在GDP结合状态下才能附着于细胞质膜，并以扩散的方式进入纤毛并富集于靠近纤毛TZ上部的部分。在此部位，ARL3被迅速激活并与纤毛膜脱离。当载有PLD的BBSome逆行于此时可与反向IFT火车分离，ARL3GTP通过与BBSome亚单位BBS1和BBS5直接结合的方式与BBSome相偶联，从而招募BBSome为其效应子以主动扩散的方式穿越纤毛TZ，达到把纤毛信号分子PLD输出纤毛以维持其纤毛内动态平衡的目的。该研究同时发现BBSome在纤毛TZ区并不是都与反向IFT火车分离从而以扩散的方式穿越纤毛TZ以输出纤毛，表明具体的纤毛信号分子以IFT的方式还是以扩散方式穿越纤毛过渡区以输出纤毛这一过程是选择性的。依赖于ARL3介导的外向BBSome纤毛过渡区扩散机制的PLD纤毛输出示意图天津科技大学樊振川教授为论文的通讯作者，天津科技大学生物工程学院刘雁霞博士后为论文的第一作者，天津科技大学食品学院博士生孙维越、张瑞凯和李文娟，天津科技大学生物工程学院博士后薛斌（现为浙江工业大学生物工程学院副研究员）和天津科技大学生物工程学院谢希贤教授参与了研究工作。本研究得到了国家自然科学基金和中国博士后科学基金的支持。