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

Abstract

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