title: Single nucleotide polymorphisms in the dystroglycan gene do not correlate with disease severity in hereditary inclusion body myopathy.
abstract: 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.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda MD, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Gottlieb
authors.forename: Carla
authors.initials: C
authors.lastname: Ciccone
authors.forename: Daniel
authors.initials: D
authors.lastname: Darvish
authors.forename: Shahrouz
authors.initials: S
authors.lastname: Naiem-Cohen
authors.forename: Marinos C
authors.initials: MC
authors.lastname: Dalakas
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Savelkoul
authors.forename: Donna M
authors.initials: DM
authors.lastname: Krasnewich
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
mesh_terms: 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
chemical_list: D017931:DNA Primers; D049030:Dystroglycans