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

Christopher J. Record; Antoinette O'Connor; Nienke E. Verbeek; Wouter van Rheenen; Eleni Zamba Papanicolaou; Stojan Peric; Peter C. Ligthart; Mariola Skorupinska; Ellen van Binsbergen; Philippe M. Campeau; Vukan Ivanovic; Brian Hennigan; John C. McHugh; Julian C. Blake; Yoshiko Murakami; Matilde Laura; Sinéad M. Murphy; Mary M. Reilly

doi:10.1002/ana.27113

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

Christopher J. Record, Antoinette O'Connor, Nienke E. Verbeek, Wouter van Rheenen, Eleni Zamba Papanicolaou, Stojan Peric, Peter C. Ligthart, Mariola Skorupinska, Ellen van Binsbergen, Philippe M. Campeau, Vukan Ivanovic, Brian Hennigan, John C. McHugh, Julian C. Blake, Yoshiko Murakami, Matilde Laura, Sinéad M. Murphy, Mary M. Reilly^*

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	388-396
Number of pages	9
Journal	Annals of Neurology
Volume	97
Issue number	2
Early online date	23 Oct 2024
DOIs	https://doi.org/10.1002/ana.27113
Publication status	Published - Feb 2025

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Annals of Neurology - 2024 - Record - Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block Final published version, 3.51 MBLicence: CC BY

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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, 97(2), 388-396. https://doi.org/10.1002/ana.27113

@article{f7ede5fcfc514d67839ea2de5a4e69a5,

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

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.",

author = "Record, {Christopher J.} and Antoinette O'Connor and Verbeek, {Nienke E.} and {van Rheenen}, Wouter and {Zamba Papanicolaou}, Eleni and Stojan Peric and Ligthart, {Peter C.} and Mariola Skorupinska and {van Binsbergen}, Ellen and Campeau, {Philippe M.} and Vukan Ivanovic and Brian Hennigan and McHugh, {John C.} and Blake, {Julian C.} and Yoshiko Murakami and Matilde Laura and Murphy, {Sin{\'e}ad M.} and Reilly, {Mary M.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2025",

month = feb,

doi = "10.1002/ana.27113",

language = "English",

volume = "97",

pages = "388--396",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley & Sons Inc.",

number = "2",

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Record, CJ, O'Connor, A, Verbeek, NE , van Rheenen, W, Zamba Papanicolaou, E, Peric, S, Ligthart, PC, Skorupinska, M, van Binsbergen, E, Campeau, PM, Ivanovic, V, Hennigan, B, McHugh, JC, Blake, JC, Murakami, Y, Laura, M, Murphy, SM & Reilly, MM 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

TY - JOUR

T1 - Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures

T2 - Expanding the Phenotype

AU - Record, Christopher J.

AU - O'Connor, Antoinette

AU - Verbeek, Nienke E.

AU - van Rheenen, Wouter

AU - Zamba Papanicolaou, Eleni

AU - Peric, Stojan

AU - Ligthart, Peter C.

AU - Skorupinska, Mariola

AU - van Binsbergen, Ellen

AU - Campeau, Philippe M.

AU - Ivanovic, Vukan

AU - Hennigan, Brian

AU - McHugh, John C.

AU - Blake, Julian C.

AU - Murakami, Yoshiko

AU - Laura, Matilde

AU - Murphy, Sinéad M.

AU - Reilly, Mary M.

PY - 2025/2

Y1 - 2025/2

N2 - 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.

AB - 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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DO - 10.1002/ana.27113

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C2 - 39444079

AN - SCOPUS:85207158643

SN - 0364-5134

VL - 97

SP - 388

EP - 396

JO - Annals of Neurology

JF - Annals of Neurology

IS - 2

ER -

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

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