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Related Concept Videos

Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
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Related Experiment Video

Updated: Jun 7, 2026

Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy
10:30

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Familial dystroglycanopathy: same mutation, different phenotypes.

Satish V Khadilkar1, Shamisha Shashank Khade2, Jharna P Mahajan Bhanushali2,3

  • 1Neurology, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India khadilkarsatish@gmail.com.

Practical Neurology
|June 5, 2026
PubMed
Summary
This summary is machine-generated.

Genetic mutations in GMPPB can cause overlapping muscular dystrophy and neuromuscular junction disorders. This study highlights how the same mutation leads to diverse clinical presentations and treatment responses in siblings, emphasizing the need for broader diagnostic considerations.

Keywords:
MUSCULAR DYSTROPHYMYASTHENIANEUROGENETICSNEUROMUSCULAR

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Area of Science:

  • Genetics
  • Neurology
  • Biochemistry

Background:

  • Limb-girdle weakness with elevated creatine kinase (CK) typically suggests muscular dystrophy.
  • However, treatable neuromuscular junction disorders can mimic these symptoms.
  • Mutations in GDP-mannose pyrophosphorylase B (GMPPB) disrupt glycosylation, affecting both dystroglycan stability and acetylcholine receptor assembly, bridging dystroglycanopathies and congenital myasthenic syndromes.

Purpose of the Study:

  • To describe the diverse clinical and therapeutic phenotypes in siblings with the same homozygous GMPPB pathogenic variant.
  • To illustrate the diagnostic challenge posed by overlapping muscular and neuromuscular junction disorders.
  • To emphasize the importance of considering neuromuscular transmission defects in limb-girdle weakness with hyperCKaemia.

Main Methods:

  • Clinical case description of two siblings with a homozygous GMPPB pathogenic variant.
  • Assessment of clinical presentation, including fatigable weakness, myopathic features, and CK levels.
  • Evaluation of response to therapeutic agents (pyridostigmine, β-adrenergic agents).
  • Electrophysiological studies, including repetitive nerve stimulation.

Main Results:

  • Siblings shared the same homozygous GMPPB variant but exhibited distinct phenotypes.
  • Brother: Fatigable proximal weakness improved with pyridostigmine.
  • Sister: Myopathic features, elevated CK, minimal response to pyridostigmine, but improved with β-adrenergic agents.
  • Both showed significant decrements on repetitive nerve stimulation.

Conclusions:

  • The GMPPB gene mutation can lead to a wide spectrum of clinical presentations, from myopathic features to treatable neuromuscular junction defects.
  • Contrasting phenotypes in siblings underscore the genetic and possibly epigenetic factors influencing disease expression.
  • Limb-girdle weakness and hyperCKaemia warrant investigation for treatable neuromuscular transmission disorders, not solely muscular dystrophies.