Single nucleotide polymorphisms in the dystroglycan gene do not correlate with disease severity in hereditary inclusion body myopathy.
Aberrant glycosylation of dystroglycan occurs in certain muscular dystrophies, including hereditary inclusion body myopathy (HIBM). HIBM harbors a widely varying clinical severity and age of onset, which raised the suspicion of the presence of disease modifier genes. We considered the highly polymorphic dystroglycan gene (DAG1) as a feasible candidate modifier gene. DAG1 genomic DNA was sequenced for 32 HIBM patients, mainly of Persian-Jewish descent. Five novel DAG1 single nucleotide polymorphisms (SNPs) were identified, bringing the total number of SNPs to 19. However, no direct correlation between DAG1 SNPs and clinical severity of HIBM could be detected. Several identified SNPs substitute an amino acid and might modulate dystroglycan function or glycosylation status, and deserve further research. These data are valuable for future studies on the role of DAG1 in HIBM and other muscular dystrophies, especially those dystrophies that involve abnormal glycosylation of dystroglycan.
Gottlieb
Emily
E
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda MD, USA.
Ciccone
Carla
C
Darvish
Daniel
D
Naiem-Cohen
Shahrouz
S
Dalakas
Marinos C
MC
Savelkoul
Paul J
PJ
Krasnewich
Donna M
DM
Gahl
William A
WA
Huizing
Marjan
M
D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D017931:DNA Primers; D049030:Dystroglycans / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
D017931:DNA Primers; D049030:Dystroglycans