{
  "abstract": "OBJECTIVE: Glycosylphosphatidylinositol (GPI)-anchored proteins play critical roles in nervous system function. Pathogenic variants in genes involved in GPI-anchor biosynthesis cause early-onset multisystem disorders known as inherited GPI deficiencies. We describe a novel neuromuscular phenotype associated with PIGB deficiency. METHODS: Patients with neuromuscular disease carrying PIGB variants were identified, and clinical data collected. GPI-anchored protein and free-GPI expression were assessed by flow cytometry and variants validated in a PIGB knockout cellular model. RESULTS: Biallelic PIGB variants were identified in 12 patients (median age 32 years, range 15-52 years) from 9 independent families. Of 15 variants, 13 were novel, including a de novo inversion generating a PIGB::RAB27A gene fusion. Of 12 patients, 10 presented with distal lower-limb weakness, and neurophysiological studies demonstrated a motor-predominant neuropathy with frequent conduction blocks in all patients. Signs of nerve hyperexcitability were observed in 9 patients, with electromyography neuromyotonic discharges and myokymia compatible with peripheral nerve hyperexcitability in 6. A total of 3 patients showed a decremental response on repetitive nerve stimulation; 2 were symptomatic and responded to pyridostigmine, consistent with neuromuscular junction transmission defect. Neurodevelopmental features were inconsistent. Flow cytometry revealed variable reductions of GPI-anchored proteins, but consistent reduction of free GPI in blood cells. Novel variants impaired GPI-anchor expression in vitro. INTERPRETATION: We expand the phenotypic spectrum of inherited GPI deficiencies with a novel neuromuscular syndrome encompassing motor neuropathy with conduction blocks, peripheral nerve hyperexcitability, and occasional neuromuscular junction defects associated with PIGB variants. PIGB and other GPI-anchor biosynthesis genes should be considered in motor neuropathy with conduction blocks. ANN NEUROL 2026.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 35,
  "authors": [
    {
      "name": "Gorka Fernández-Eulate"
    },
    {
      "name": "Romain Duval"
    },
    {
      "name": "Marina Konyukh"
    },
    {
      "name": "Alessandro Bertini"
    },
    {
      "name": "Ayse Candayan"
    },
    {
      "name": "Albena Jordanova"
    },
    {
      "name": "Theresa Brunet"
    },
    {
      "name": "Wolfgang Müller-Felber"
    },
    {
      "name": "Helena Pernice"
    },
    {
      "name": "Katrin Hahn"
    },
    {
      "name": "Nadja Ehmke"
    },
    {
      "name": "Juliane Beuschlein"
    },
    {
      "name": "Bertrand Isidor"
    },
    {
      "name": "Benjamin Cogné"
    },
    {
      "name": "Yann Péréon"
    },
    {
      "name": "Annabelle Chaussenot"
    },
    {
      "name": "John Rendu"
    },
    {
      "name": "Aysylu Murtazina"
    },
    {
      "name": "Dmitrii Subbotin"
    },
    {
      "name": "Artem Borovikov"
    },
    {
      "name": "Andrey Marakhonov"
    },
    {
      "name": "Chiara Pisciotta"
    },
    {
      "name": "Paola Saveri"
    },
    {
      "name": "Daniele Cazzato"
    },
    {
      "name": "Lucie Lemeray"
    },
    {
      "name": "Bérengère Koehl"
    },
    {
      "name": "Jean‐madeleine de Sainte-Agathe"
    },
    {
      "name": "Stefano Facchini"
    },
    {
      "name": "Ilaria Quartesan"
    },
    {
      "name": "Andrea Cortese"
    },
    {
      "name": "Yesim Parman"
    },
    {
      "name": "Arman Cakar"
    },
    {
      "name": "Davide Pareyson"
    },
    {
      "name": "Slim Azouzi"
    },
    {
      "name": "Tanya Stojkovic"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ecyr09z53b272.bib",
  "cited_by": 0,
  "doi": "10.1002/ana.78358",
  "fulltext_url": null,
  "id": "ecyr09z53b272",
  "issns": [
    "0364-5134",
    "1531-8249"
  ],
  "landing_url": "https://hal.science/hal-05786132v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2804|Hereditary Neurological Disorders"
    ]
  ],
  "openalex": "W7214925895",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.78358",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/ecyr09z53b272.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "hal-05786132",
      "source": "hal",
      "url": "https://hal.science/hal-05786132v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Hereditary Neurological Disorders",
      "subfield": "neuroscience"
    }
  ],
  "title": "Biallelic PIGB Variants Cause Motor Neuropathy with Conduction Blocks and Peripheral Nerve Hyperexcitability",
  "title_text": "Biallelic PIGB Variants Cause Motor Neuropathy with Conduction Blocks and Peripheral Nerve Hyperexcitability",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:50Z",
  "url": "https://research.draconitic.com/paper/ecyr09z53b272",
  "venue": "Annals of Neurology",
  "versions": []
}