P570: DMD testing In adult males unknown to have dystrophinopathy: A retrospective analysis from a sponsored DMD testing program*

Introduction: Dystrophinopathies are a spectrum of disorders associated with variants in the DMD gene.Historically, confirmatory genetic testing has been completed on those who exhibit a classic clinical picture.However, broader testing, either through familial cascade testing or increased recognition of "milder" phenotypes, seems to be identifying additional hemizygous individuals who receive a diagnosis or possible positive result later in life.Methods: A retrospective analysis of testing records through a sponsored genetic testing program was performed to identify XY males who underwent targeted DMD variant testing.Participants were selected for inclusion into the cohort if they met the following criteria: 1) They were over 18 years of age at the time of testing; 2) They were found to have a variant in the DMD gene that was classified as pathogenic or a variant of uncertain significance at the time of reporting; 3) They were not reported to have a clinical suspicion of or diagnosis of dystrophinopathy.Results: A total of 47 individuals meeting these criteria were identified, the majority of whom (42/47; 89.4%) reported no clinical symptoms.In 25 individuals (53.2%), the indication for testing was prompted by a daughter who had previously tested positive for the same variant.Most variants (32/47; 68.1%) were deletions of one or more exons, and the majority (38/47; 80.9%) were classified as pathogenic or likely pathogenic.The most frequently observed variant was a deletion of exons 49-51 (7/47; 14.9%), followed by a deletion of exons 48-55 (4/47; 8.5%). Conclusion:This retrospective look on targeted DMD testing documents a group of individuals who historically may not have been tested for dystrophinopathy.As genetic testing technologies continue to expand and are more widely utilized, we look to learn more about the variability of the spectrum to provide additional genotype-phenotype correlation data, along with clarifying the pathogenicity of variants identified incidentally on more broad population screening mechanisms.