High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark

Ann Neurol. 2006 May;59(5):808-15. doi: 10.1002/ana.20824.


Objectives: The prevalence of limb girdle muscular dystrophy type 2I (LGMD2I) in northern Europe is unknown. We investigated this and the genotype-phenotype relation in LGMD2I.

Methods: Prospective clinical and molecular screening of 118 Danish patients registered with LGMD was performed to divide patients into LGMD subtypes.

Results: One hundred three patients fulfilled the clinical criteria for LGMD2. Thirty-eight had LGMD2I (27 homozygous, 11 compound heterozygous for 826C>A), 23 had sarcoglycanopathy, 2 dysferlinopathy, 12 calpainopathy, and 4 Becker muscular dystrophy. The 24 patients with no molecular diagnosis did not harbor fukutin-related protein gene (FKRP) mutations. A clear clinical delineation was found between patients homozygous and compound heterozygous for the 826C>A mutation. Homozygous patients had later debut, milder clinical progression, and less muscle weakness compared with compound heterozygous patients, who were all wheelchair bound by their mid-20s. Impaired cardiac pump function was found in both groups.

Interpretation: This study reports a different distribution of LGMD subtypes in Denmark than seen in other geographic regions, with a threefold to fourfold higher prevalence of LGMD2I than elsewhere. The findings support a clear clinical delineation between patients homozygous and compound heterozygous for the 826C>A mutation in FKRP. The findings suggest that, in the studied region, screening for the 826C>A mutation will identify all persons with LGMD2I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Blotting, Western
  • Creatine Kinase / blood
  • DNA / genetics
  • Denmark / epidemiology
  • Disease Progression
  • Female
  • Gene Frequency
  • Genotype
  • Heart Function Tests
  • Heterozygote
  • Homozygote
  • Humans
  • Immunohistochemistry
  • Male
  • Muscle Weakness / epidemiology
  • Muscle Weakness / etiology
  • Muscular Dystrophies, Limb-Girdle / classification
  • Muscular Dystrophies, Limb-Girdle / epidemiology*
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation / physiology
  • Pentosyltransferases
  • Phenotype
  • Prospective Studies
  • Proteins / genetics


  • Proteins
  • DNA
  • FKRP protein, human
  • Pentosyltransferases
  • Creatine Kinase