PIGG 的隐性变异会导致具有可变传导阻滞、儿童震颤和热性惊厥的运动神经病：扩展表型。

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2024-10-23 DOI:10.1002/ana.27113

Christopher J. Record MRCP, Antoinette O'Connor MRCPI, PhD, Nienke E. Verbeek MD, PhD, Wouter van Rheenen MD, PhD, Eleni Zamba Papanicolaou MD, Stojan Peric MD, PhD, Peter C. Ligthart MSc, Mariola Skorupinska MSc, MA, Ellen van Binsbergen PhD, Philippe M. Campeau MD, FCCMG, Vukan Ivanovic MD, Brian Hennigan BSc, John C. McHugh MD, MRCPI, Julian C. Blake MRCP, Yoshiko Murakami MD, PhD, Matilde Laura MD, PhD, Sinéad M. Murphy MD, FRCPI, Mary M. Reilly MD, FRCP, FRCPI, FMedSci

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引用次数: 0

摘要

磷脂酰肌醇聚糖锚生物合成 G 类（PIGG）的双拷贝变体会导致肌张力低下、智力障碍、癫痫发作和小脑特征。我们介绍了来自 6 个家庭的 8 位患者，他们都患有儿童期发病的运动神经病变，神经生理学表现为不同的运动传导阻滞和颞叶弥散。所有患者均在儿童期发病，8 人中有 5 人有小脑受累，8 人中有 6 人在儿童期有发热性癫痫发作。所有患者都有双叶 PIGG 变异，包括之前报道的致病变异 Trp505*，以及 6 个新型变异。通过PIGO/PIGG双基因敲除系统，Val339Gly和Gly19Glu的酶活性被证明为无效，Trp505*的残余活性则是由于通读所致。1 个家庭的 Emm 阴性血型得到确认。未解决的运动神经病变应考虑 PIGG。ann neurol 2024.

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Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures: Expanding the Phenotype

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

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.