{
  "abstract": "Mutations in the pyridine nucleotide-disulfide oxide reductase domain-containing protein 1 (PYROXD1) gene are characteristically linked to early-onset congenital myofibrillar myopathy, typically presenting with generalized weakness, hypotonia, and respiratory insufficiency in infancy or early childhood. However, emerging evidence suggests phenotypic heterogeneity.\n\nWe report the case of a 45-year-old Tunisian woman, born to non-consanguineous parents, who presented with a slowly progressive limb-girdle muscular dystrophy (LGMD) phenotype; her older brother, subsequently confirmed to carry the same homozygous variant, had a similar but more severe clinical history of proximal weakness. The patient’s symptoms began at age 17 with running difficulties, progressing by age 35 to difficulty rising from a seated position and climbing stairs, and by age 45 to exertional dyspnea, dysphagia, and sleep-disordered breathing. Physical examination revealed a high-arched palate, scoliosis, joint hypermobility, limited ankle dorsiflexion, palatal weakness, and mild neck flexion weakness alongside a proximal-dominant limb-girdle pattern of weakness. Her brother showed a matching but more severe phenotype starting at age 12. Electrodiagnostic studies demonstrated normal nerve conduction and a non-irritable myopathy; serum creatine kinase was entirely normal, and pulmonary function testing revealed a restrictive ventilatory defect with mild obstructive sleep apnea on polysomnography. Clinical exome sequencing confirmed a pathogenic homozygous c.464A>G (p.Asn155Ser) mutation in the PYROXD1 gene in both affected siblings, with both parents confirmed as unaffected heterozygous carriers. This represents the first molecularly confirmed family with PYROXD1-related myopathy in Tunisia and North Africa, and only the second family identified across the African continent; a single unrelated Tunisian case harboring the same variant has also recently been reported.\n\nThis case expands the known clinical spectrum of PYROXD1 variants to include adult-onset LGMD-like presentations with respiratory and bulbar involvement, emphasizes the diagnostic utility of recognizing associated dysmorphic features (scoliosis, high-arched palate, nasal speech, and joint hypermobility), and highlights the pivotal role of comprehensive genomic testing in atypical adult myopathies.",
  "abstract_shown": true,
  "affiliations": [
    "DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Knoxville, USA",
    "Medicine, Royal College of Surgeons in Ireland - Bahrain, Busaiteen, BHR",
    "Neurosciences, Hamad Medical Corporation, Doha, QAT"
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Abraham Alhatou"
    },
    {
      "affs": [
        1
      ],
      "name": "Omar M Alhatou"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohammed Alhatou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8qq62wkpca1h7.bib",
  "cited_by": 0,
  "doi": "10.7759/cureus.117414",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728484/?tool=EBI",
  "id": "8qq62wkpca1h7",
  "issns": [
    "2168-8184"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13728484",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Internal Medicine"
    ],
    [
      "heading",
      "Neurology"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7219667880",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728484/pdf/?tool=EBI",
  "pmcid": "PMC13728484",
  "pmid": "42978920",
  "published": "2026-10-04",
  "publisher": "Cureus Inc.",
  "ris": "https://research.draconitic.com/paper/8qq62wkpca1h7.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:45Z",
      "native_id": "PMC:PMC13728484",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13728484"
    },
    {
      "first_seen": "2026-11-07T12:21:27Z",
      "native_id": "PMC13728484",
      "source": "pmc",
      "url": "https://doi.org/10.7759/cureus.117414"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "heading:Neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Adult-Onset Limb-Girdle Phenotype Associated With a Homozygous PYROXD1 Variant: The Case of a North African Family",
  "title_text": "Adult-Onset Limb-Girdle Phenotype Associated With a Homozygous PYROXD1 Variant: The Case of a North African Family",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:27Z",
  "url": "https://research.draconitic.com/paper/8qq62wkpca1h7",
  "venue": "Cureus",
  "versions": []
}