Cognitively Affected DMD Patients have Unique Methylation Signatures Compared to Cognitively Normal DMD Patients

The overarching goal of this project was to identify changes in methylation patterns in Duchenne muscular dystrophy (DMD) patients with discordant symptoms using whole genome bisulfite sequencing (WGBS) from genomic DNA isolated from whole serum. DMD siblings (biological brothers) had the same genetic mutation in the dystrophin gene but with discordance in symptoms such as ambulation, cardiopulmonary function, and cognition. Trios (DMD sibling brothers and biological mother or father) and quartets (DMD sibling brothers and biological mother and father) were recruited for this study for intra- and inter-familial comparisons of the methylation of gene bodies.]]>
Inclusion Criteria DMD males only, over the age of 4 years old with genetically confirmed dystrophin mutations DMD siblings have to have the same dystrophin mutation and consent to research studies Biological siblings and parents up to age 70 were required and the parents could be carriers Exclusion Criteria Any intermediate DMD and/or Becker muscular dystrophy (BMD) patients were excluded as were step siblings or parents ]]>
Approximately 13 samples were recruited from 5 separate patient families. Quartets and trios of affected DMD sibling brothers and their biological parents were recruited and fully-consented for genomic research. All samples were de-identified at the time of consent and access was restricted to a secure REDCAP database. Patient families were recruited upon a routine visit to the Muscular Dystrophy Clinic at Children's of Alabama. After consent, blood was drawn (no more than 3 ml) by a nurse or phlebotomist and stored in PAXgene tubes before genomic DNA isolation at a later time point by the UAB CCTS Specimen Processing and Biorepository Core facility. Genomic DNA was then shipped to the HudsonAlpha Genome Sequencing Center for whole genome bisulfite sequencing. Bioinformatics was performed by the UAB Biological Data Science Core. Additional subjects were recruited and some data was not submitted based on the ability to obtain additional family members. ]]>