{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T19:04:41Z","timestamp":1783191881088,"version":"3.54.6"},"reference-count":14,"publisher":"BMJ","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Pract Neurol"],"accepted":{"date-parts":[[2026,5,19]]},"abstract":"<jats:p>\n                    Patients presenting with limb-girdle weakness and elevated creatine kinase (CK) are usually assumed to have a primary muscular dystrophy. Occasionally, however, a treatable neuromuscular junction disorder may be hidden within this presentation. Mutations in\n                    <jats:italic>GMPPB<\/jats:italic>\n                    (GDP-mannose pyrophosphorylase B) disrupt glycosylation pathways required both for \u03b1-dystroglycan stability and acetylcholine receptor assembly, creating such an unusual overlap between dystroglycanopathy and congenital myasthenic syndrome. We describe two siblings who carry the same homozygous\n                    <jats:italic>GMPPB<\/jats:italic>\n                    pathogenic variant but presented with markedly different clinical and therapeutic profiles. The brother developed fatigable proximal weakness that showed a striking and sustained improvement with pyridostigmine. His sister, however, presented with prominent myopathic features and markedly elevated CK, minimal response to cholinergic therapy but improvement with \u03b2-adrenergic agents. Both siblings showed a significant decrement in repetitive nerve stimulation. These contrasting phenotypes illustrate the remarkable clinical diversity resulting from the same mutation and emphasise an important diagnostic lesson: patients presenting with limb-girdle weakness and hyperCKaemia may still harbour a treatable defect of neuromuscular transmission.\n                  <\/jats:p>","DOI":"10.1136\/pn-2026-005222","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:20:30Z","timestamp":1780680030000},"page":"pn-2026-005222","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Familial dystroglycanopathy: same mutation, different phenotypes"],"prefix":"10.1136","author":[{"given":"Satish V","family":"Khadilkar","sequence":"first","affiliation":[{"name":"Neurology, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamisha Shashank","family":"Khade","sequence":"additional","affiliation":[{"name":"Neurology, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jharna P","family":"Mahajan (Bhanushali)","sequence":"additional","affiliation":[{"name":"Neurology, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India"},{"name":"Neurology, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"2026060510201802000_pn-2026-005222v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.009"},{"key":"2026060510201802000_pn-2026-005222v1.2","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1093\/brain\/awv185","article-title":"Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies","volume":"138","author":"Belaya","year":"2015","journal-title":"Brain (Bacau)"},{"key":"2026060510201802000_pn-2026-005222v1.3","doi-asserted-by":"crossref","DOI":"10.3390\/genes14020372","article-title":"GDP-Mannose Pyrophosphorylase B (GMPPB)-Related Disorders","volume":"14","author":"Chompoopong","year":"2023","journal-title":"Genes (Basel)"},{"key":"2026060510201802000_pn-2026-005222v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-021-00658-1"},{"key":"2026060510201802000_pn-2026-005222v1.5","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1093\/brain\/awv013","article-title":"Expanding the phenotype of GMPPB mutations","volume":"138","author":"Cabrera-Serrano","year":"2015","journal-title":"Brain (Bacau)"},{"key":"2026060510201802000_pn-2026-005222v1.6","first-page":"275","article-title":"Limb-girdle muscular dystrophy due to GMPPB mutations: A case report and comprehensive literature review","volume":"20","author":"Sun","year":"2020","journal-title":"Bosn J of Basic Med Sci"},{"key":"2026060510201802000_pn-2026-005222v1.7","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1212\/WNL.0000000000001440","article-title":"Intrafamilial variability in GMPPB-associated dystroglycanopathy: Broadening of the phenotype","volume":"84","author":"Bharucha-Goebel","year":"2015","journal-title":"Neurology (ECronicon)"},{"key":"2026060510201802000_pn-2026-005222v1.8","first-page":"100","article-title":"Clinical and molecular spectrum of GMPPB-related disorders","volume":"27","author":"Tian","year":"2017","journal-title":"Neuromuscul Disord"},{"key":"2026060510201802000_pn-2026-005222v1.9","doi-asserted-by":"publisher","DOI":"10.1136\/pn-2023-003838"},{"key":"2026060510201802000_pn-2026-005222v1.10","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/ncn3.12700","article-title":"Congenital myasthenic syndromes: A study of 15 cases","volume":"11","author":"Khadilkar","year":"2023","journal-title":"Neurology & Clinical Neurosc"},{"key":"2026060510201802000_pn-2026-005222v1.11","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2017-001598"},{"key":"2026060510201802000_pn-2026-005222v1.12","doi-asserted-by":"publisher","DOI":"10.1136\/pn-2025-004528"},{"key":"2026060510201802000_pn-2026-005222v1.13","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.nmd.2020.07.009","article-title":"Early and long-term effect of the treatment with pyridostigmine in patients with GMPPB-related congenital myasthenic syndrome","volume":"30","author":"Bobadilla-Quesada","year":"2020","journal-title":"Neuromuscul Disord"},{"key":"2026060510201802000_pn-2026-005222v1.14","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181dd43bf"}],"container-title":["Practical Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/pn-2026-005222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:20:31Z","timestamp":1780680031000},"score":1,"resource":{"primary":{"URL":"https:\/\/pn.bmj.com\/lookup\/doi\/10.1136\/pn-2026-005222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":14,"alternative-id":["10.1136\/pn-2026-005222"],"URL":"https:\/\/doi.org\/10.1136\/pn-2026-005222","relation":{},"ISSN":["1474-7758","1474-7766"],"issn-type":[{"value":"1474-7758","type":"print"},{"value":"1474-7766","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}