Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.
Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.
复制标题
DOI：
10.1093/braincomms/fcad222
复制
发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
LNPK编码一种保守的膜蛋白，其稳定在多种生物学功能中起关键作用的管状内质网网络的连接。最近，LNPK的纯合子变体显示在4名患者中引起神经发育障碍（OMIM#618090），所述患者显示发育迟缓、癫痫和非特异性脑畸形，包括胼胝体发育不全和小脑的可变损伤。我们试图描绘LNPK相关疾病的分子和表型谱。对11个家系进行了外显子组或基因组测序。对所有受影响的个体进行了全面的临床和神经放射学评估，包括对先前报告的患者进行审查。我们在16名表现为中度至重度发育迟缓、认知障碍、退化、难治性癫痫和可识别的神经影像学模式（包括胼胝体发育不全和小产钳信号改变）的个体中鉴定出12种不同的纯合子功能丧失变体（“猞猁耳”征）、与黑质信号改变相关的小脑萎缩、轻度脑萎缩、短中脑和小脑发育不全/萎缩。总之，我们定义了LNPK相关疾病的核心表型，并扩展了表现为“猞猁耳”征的神经系统疾病的列表，这表明可能存在与内质网吞噬功能障碍相关的共同潜在机制。在这项研究中，Accogli等人描述了LNPK相关神经发育障碍的分子和临床谱，伴有退行性病程，其特征为可识别的神经影像学模式，包括胼胝体发育不全和小镊子信号改变（“猞猁耳”征），表明与内质网吞噬功能障碍相关的病理机制。
LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor (‘ear-of-the-lynx’ sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the ‘ear-of-the-lynx’ sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction. In this study, Accogli et al. delineate the molecular and clinical spectrum of LNPK-related neurodevelopmental disorder with degenerative course, characterized by a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor (‘ear-of-the-lynx’ sign), suggesting a pathomechanism related to endoplasmic reticulum-phagy dysfunction.
登录
查看更多内容
DOI：
10.1007/s00018-015-2052-6
发表时间：
2016-01
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Schwarz DS;Blower MD
通讯作者：
Blower MD
DOI：
10.1073/pnas.1423026112
发表时间：
2015-01-13
影响因子：
11.1
作者：
Chen, Shuliang;Desai, Tanvi;Novick, Peter J.
通讯作者：
Novick, Peter J.
影响因子：
4
作者：
Saenz-Farret, Michel;Lang, Anthony E.;Zuniga-Ramirez, Carlos
通讯作者：
Zuniga-Ramirez, Carlos
影响因子：
11
作者：
Yamamoto YH;Noda T
通讯作者：
Noda T
影响因子：
4
作者：
Agarwal, Ayush;Oinam, Rahul;Srivastava, Achal K.
通讯作者：
Srivastava, Achal K.