Prevalence, mutation spectrum and phenotypic variability in Norwegian patients with Limb Girdle Muscular Dystrophy 2I.
Mutations in the FKRP (Fukutin Related Protein) gene produce a range of phenotypes including Limb Girdle Muscular Dystrophy Type 2I (LGMD2I). In order to investigate the prevalence, the mutation spectrum and possible genotype-phenotype correlation, we studied a cohort of Norwegian patients with LGMD2I, ascertained in a 4-year period. In this retrospective study of genetically tested patients, we identified 88 patients from 69 families, who were either homozygous or compound heterozygous for FKRP mutations. This gives a minimum prevalence of 1/54,000 and a corresponding carrier frequency of 1/116 in the Norwegian population. Seven different FKRP mutations, including three novel changes, were detected. Seventy-six patients were homozygous for the common c.826C>A mutation. These patients had later disease onset than patients who were compound heterozygous - 14.0 vs. 6.1 years. We detected substantial variability in disease severity among homozygous patients.
Stensland
Eva
E
Department of Habilitation, University Hospital of North Norway, Tromsø, Norway. eva.stensland@unn.no
Lindal
Sigurd
S
Jonsrud
Christoffer
C
Torbergsen
Torberg
T
Bindoff
Laurence A
LA
Rasmussen
Magnhild
M
Dahl
Arve
A
Thyssen
Frances
F
Nilssen
Øivind
Ø
D000328:Adult; D017668:Age of Onset; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009664:Norway / Q000453:epidemiology; D010430:Pentosyltransferases; D010641:Phenotype; D015995:Prevalence; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
D011506:Proteins; C443107:FKRP protein, human; D010430:Pentosyltransferases