Recessive Variants in <scp><i>PIGG</i></scp> 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.
Authors
- Yoshiko Murakami (ORCID: https://orcid.org/0000-0002-4870-5734)
- Vukan Ivanović (ORCID: https://orcid.org/0000-0002-8542-9441)
- Christopher J. Record (ORCID: https://orcid.org/0000-0002-9802-2683)
- John C. McHugh (ORCID: https://orcid.org/0000-0001-7726-7553)
- Mary M. Reilly (ORCID: https://orcid.org/0000-0003-0686-905X)
- Mariola Skorupinska
- Antoinette O’Connor (ORCID: https://orcid.org/0000-0003-4467-128X)
- Matilde Laurá (ORCID: https://orcid.org/0000-0001-8264-8676)
- Ellen van Binsbergen
- Peter C. Ligthart
- Sinéad M. Murphy (ORCID: https://orcid.org/0000-0002-7277-414X)
- Wouter van Rheenen (ORCID: https://orcid.org/0000-0002-5860-1533)
- Nienke E. Verbeek
- Philippe M. Campeau (ORCID: https://orcid.org/0000-0001-9713-7107)
- Eleni Zamba Papanicolaou
- Stojan Peric
- Julian Blake
- Brian Hennigan
Institutions
- Utrecht University (NL)
- Trinity College Dublin (IE)
- Norfolk and Norwich University Hospital (GB)
- Tallaght University Hospital (IE)
- Children's Health Ireland at Crumlin (IE)
- University Medical Center Utrecht (NL)
- Sanquin (NL)
- University of Belgrade (RS)
- Univerzitetski Klinički Centar Srbije (RS)
- Sociedad Hispano Mundial (ES)
- National Hospital for Neurology and Neurosurgery (GB)
- University College London (GB)
- Cyprus Institute of Neurology and Genetics (CY)
- Université de Montréal (CA)
- The University of Osaka (JP)
Publication Details
- Journal
- Annals of Neurology
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1002/ana.27113
- Citations
- 1
- Primary Topic
- Trypanosoma species research and implications
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- Charcot-Marie-Tooth Association
- Muscular Dystrophy Association
- Japan Agency for Medical Research and Development
- Wellcome Trust
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- University College London
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Prinses Beatrix Spierfonds
- Medical Research Council