Record Christopher J, O'Connor Antoinette, Verbeek Nienke E, van Rheenen Wouter, Zamba Papanicolaou Eleni, Peric Stojan, Ligthart Peter C, Skorupinska Mariola, van Binsbergen Ellen, Campeau Philippe M, Ivanovic Vukan, Hennigan Brian, McHugh John C, Blake Julian C, Murakami Yoshiko, Laura Matilde, Murphy Sinéad M, Reilly Mary M
Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Department of Neurology, Tallaght University Hospital, Dublin, Ireland.
Ann Neurol. 2025 Feb;97(2):388-396. doi: 10.1002/ana.27113. Epub 2024 Oct 23.
Biallelic variants in phosphatidylinositol glycan anchor biosynthesis, class G (PIGG) cause hypotonia, intellectual disability, seizures, and cerebellar features. We present 8 patients from 6 families with a childhood-onset motor neuropathy and neurophysiology demonstrating variable motor conduction block and temporal dispersion. All individuals had a childhood onset tremor, 5 of 8 had cerebellar involvement, and 6 of 8 had childhood febrile seizures. All individuals have biallelic PIGG variants, including the previously reported pathogenic variant Trp505*, plus 6 novel variants. Null enzyme activity is demonstrated via PIGO/PIGG double knockout system for Val339Gly and Gly19Glu, and residual activity for Trp505* due to read-through. Emm negative blood group status was confirmed in 1 family. PIGG should be considered in unsolved motor neuropathy. ANN NEUROL 2025;97:388-396.
磷脂酰肌醇聚糖锚定生物合成G类（PIGG）双等位基因变异可导致肌张力减退、智力残疾、癫痫发作和小脑特征。我们报告了来自6个家庭的8例患者，他们患有儿童期起病的运动神经病，神经生理学检查显示有可变的运动传导阻滞和时间离散。所有个体均有儿童期起病的震颤，8例中有5例有小脑受累，8例中有6例有儿童期热性惊厥。所有个体均有双等位基因PIGG变异，包括先前报道的致病性变异Trp505*，以及6种新变异。通过PIGO/PIGG双敲除系统证实Val339Gly和Gly19Glu无酶活性，而Trp505*因通读而有残余活性。在1个家庭中证实了Emm阴性血型状态。对于未解决的运动神经病，应考虑PIGG基因。《神经病学纪事》2025年；97:388 - 396。
