Molecular diagnosis of Duchenne muscular dystrophy: Best practices and guidelines for molecular testing and test results reporting with advent of molecular therapies

MADHURI HEGDE; FLORENCIA GILIBERTO,; MITCHELL BAILEY; ANNEMIEKE AARTSMA-RUS; NICOLE MILLER

Barcelona

Congreso; The European Society of Human Genetics (ESHG) annual conference; 2016

The European Society of Human Genetics (ESHG)

■■Duchenne muscular dystrophy (Duchenne/DMD) and Becker muscular dystrophy(Becker/BMD) are caused by pathogenic variants in the DMD gene encoding thedystrophin protein (OMIM #310200, #300376)?? Duchenne/DMD is the more severe form of disease, and results from a loss ofproduction of functional dystrophin■■Most common Duchenne/DMD-causing DMD variants reported in TREAT-NMD1:?? Large deletions/duplications = 79% (deletions = 68%, duplications = 11%)?? Small mutations = 20% (small del/dup, nonsense [10%], missense, splice site)■■Molecular diagnosis of Duchenne/DMD commonly follows 2-tiered, moleculartesting:?? First tier?deletion/duplication?? Second tier?sequencing, if no deletion/duplication identified■■Precise determination of the DMD molecular defect is becoming crucial for accuratedetermination of patient eligibility for molecular therapies in development, such asexon skipping and nonsense mutation DMD therapiesMethods■■In 2015, 27 international DMD experts met to discuss current vs future bestpractices in Duchenne/DMD molecular diagnostic testing and test results reporting?? Experts were molecular and clinical geneticists, research scientists, or geneticcounselors from Europe (10), North America (9), South America (5), and theAsia-Pacific region (3)■■A comprehensive survey was also completed by 20 diagnostic laboratories experts