Durmus Hacer, Mertoğlu Elif, Sticht Heinrich, Ceylaner Serdar, Kulaksızoğlu Işın Baral, Hashemolhosseini Said, Uçar Evren Önay, Parman Yesim
Department of Neurology, Faculty of Medicine, Istanbul University, 34390, Capa, Istanbul, Turkey.
Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul, Turkey.
Neurol Sci. 2021 Sep;42(9):3871-3878. doi: 10.1007/s10072-021-05100-w. Epub 2021 Feb 2.
The protein "ADP-Ribosylarginine Hydrolase-Like Protein 2" is encoded by ADPRHL2 and reverses ADP-ribosylation. Recently, mutations in ADPRHL2 were found to be associated with a very rare childhood onset severe neurodegeneration syndrome with episodic, stress-induced seizures, ataxia, and axonal neuropathy. In this study, we evaluate a novel mutation in ADPRHL2 leading to an unknown adult onset syndrome "episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome)."
DESIGN/METHODS: Four patients with episodic psychosis, ataxia, and motor neuropathy with pyramidal signs were included in this study.
An index patient presented ataxia, postural tremor in the hands, and hallucinations at age 20 years, which had started after a viral infection. She improved within 3 months without any treatment. Her neurological exam revealed mild distal weakness, brisk DTRs, bilateral Babinski sign, impaired vibration sensation, position, and ataxia. Pes cavus and hammer toes were also noted. EMG revealed neurogenic changes in distal muscles and normal sensory nerve conduction studies. Cranial MRI was normal. She had three more severe episodes in recent years, and her neurologic findings got progressively worse. Two of her older sisters had much milder phenotypes. The phenotype of the fourth patient from an unrelated family was identical with the index patient. All affected patients had homozygous novel NM_017825.3:c.838G>A (p.Ala280Thr) mutations in a highly conserved region of ADPRHL2. Western blot analyses demonstrated that ADPRHL2 was not expressed in these patients.
Here, we describe a novel mutation in ADPRHL2, which further expands the phenotypic and genetic spectrum of the patients harboring these mutations.
“ADP-核糖基精氨酸水解酶样蛋白2”由ADPRHL2编码，可逆转ADP-核糖基化。最近发现，ADPRHL2突变与一种非常罕见的儿童期起病的严重神经退行性综合征相关，该综合征伴有发作性、应激性癫痫、共济失调和轴索性神经病。在本研究中，我们评估了ADPRHL2中的一种新突变，该突变导致一种未知的成人起病综合征“发作性精神病、共济失调、伴有锥体束征的运动神经病（PAMP综合征）”。
设计/方法：本研究纳入了4例患有发作性精神病、共济失调和伴有锥体束征的运动神经病的患者。
一名索引患者在20岁时出现共济失调、手部姿势性震颤和幻觉，这些症状在病毒感染后开始出现。未经任何治疗，她在3个月内病情好转。她的神经系统检查显示轻度远端肌无力、腱反射亢进、双侧巴宾斯基征、振动觉、位置觉受损以及共济失调。还发现了高弓足和槌状趾。肌电图显示远端肌肉有神经源性改变，感觉神经传导研究正常。头颅磁共振成像正常。近年来，她又发作了3次更严重的病情，神经学检查结果逐渐恶化。她的两个姐姐表型要轻得多。来自一个无关家族的第四名患者的表型与索引患者相同。所有受影响的患者在ADPRHL2的一个高度保守区域均存在纯合的新突变NM_017825.3:c.838G>A（p.Ala280Thr）。蛋白质免疫印迹分析表明，这些患者中未表达ADPRHL2。
在此，我们描述了ADPRHL2中的一种新突变，这进一步扩展了携带这些突变患者的表型和基因谱。
