Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures: Expanding the Phenotype
Publication date
2025-02
Authors
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.
Editors
Advisors
Supervisors
Document Type
Article
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Abstract
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.
Keywords
Neurology, Clinical Neurology
Citation
Record, C J, O'Connor, A, Verbeek, N E, van Rheenen, W, Zamba Papanicolaou, E, Peric, S, Ligthart, P C, Skorupinska, M, van Binsbergen, E, Campeau, P M, Ivanovic, V, Hennigan, B, McHugh, J C, Blake, J C, Murakami, Y, Laura, M, Murphy, S M & Reilly, M M 2025, 'Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures : Expanding the Phenotype', Annals of Neurology, vol. 97, no. 2, pp. 388-396. https://doi.org/10.1002/ana.27113