Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.
Limb girdle muscular dystrophy (LGMD) is very common in the Hutterite population of the North American Prairies. We have recently reported the homozygous c.1459G>A mutation in TRIM32 associated with LGMD2H. We have also identified Hutterite patients with LGMD2I, homozygous for the common c.826C>A mutation in FKRP. To date, all Hutterites with LGMD have been shown to be homozygous for either the TRIM32 or FKRP mutation. We now report a Hutterite family in which both parents and five sons were all found to be homozygous for the TRIM32 mutation. The father had slowly progressive proximal muscle weakness, whereas three sons and their mother, all currently asymptomatic, had normal physical examinations. The remaining two sons (7 and 10 years old), presented with mild decrease in stamina, had normal neuromuscular examinations and were found to be homozygous for the FKRP mutation in addition to the TRIM32 mutation. These two boys do not differ in age at or mode of presentation, physical findings, or serum CK levels compared to age-matched individuals affected with LGMD2I alone. This suggests that the effects of these two mutations are not acting synergistically at this time. It remains to be seen whether there will be signs of interaction between these two mutations as the patients get older.
Frosk
Patrick
P
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada.
Del Bigio
Marc R
MR
Wrogemann
Klaus
K
Greenberg
Cheryl R
CR
D000328:Adult; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010430:Pentosyltransferases; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D035781:Siblings; D014157:Transcription Factors / Q000235:genetics; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D011506:Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases; C443107:FKRP protein, human; D010430:Pentosyltransferases