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

• Published in: Annals of neurology
• Main 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, Ivanovic, Vukan, Hennigan, Brian, McHugh, John C, Blake, Julian C, Murakami, Yoshiko, Laura, Matilde, Murphy, Sinéad M, Reilly, Mary M
• Format: Journal Article
• Language: English
• Published: United States 23-10-2024
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.27113

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 2024.