Significance of incidental copy number variants in the Duchenne muscular dystrophy gene

Ginjaar, I.B.; Kriek, M.; Hoffer, M.J.V.; Oegema, R.; Binsbergen, E. van; Diderich, K.E.M.; Zutven, L.J.C.M. van; Duijkers, F.A.M.; Knegt, A.C.; Erasmus, C.E.; Leeuw, N. de; Verheij, J.B.G.M.; Dijkhuizen, T.; Duyvenvoorde, H.A. van

doi:doi:10.1016/j.nmd.2025.106219

We report results of laboratory and clinical investigations in 32 cases with incidental findings of large, intragenic deletions and gains in the huge Duchenne muscular dystrophy gene using microarray analysis. The patients and prenatal cases were referred for various reasons unrelated to DMD. Multiplex Ligation-dependent Probe Amplification of the DMD gene confirmed and refined deletions (19/32) and duplications (13/32). In 18 of the 32 cases a dystrophinopathy diagnosis could be established; 10 males were found to have dystrophinopathy and eight females were diagnosed as carriers. Sixteen of them had a pathogenic deletion and two had a pathogenic duplication. In three of the 32 cases the variants remained of unknown significance. In one of the 32 cases dystrophinopathy could be excluded. In the remaining 10 cases, the variant was likely benign. Our results show the importance of additional genetic analyses and clinical follow up after potentially incidental findings of copy number...Show moreWe report results of laboratory and clinical investigations in 32 cases with incidental findings of large, intragenic deletions and gains in the huge Duchenne muscular dystrophy gene using microarray analysis. The patients and prenatal cases were referred for various reasons unrelated to DMD. Multiplex Ligation-dependent Probe Amplification of the DMD gene confirmed and refined deletions (19/32) and duplications (13/32). In 18 of the 32 cases a dystrophinopathy diagnosis could be established; 10 males were found to have dystrophinopathy and eight females were diagnosed as carriers. Sixteen of them had a pathogenic deletion and two had a pathogenic duplication. In three of the 32 cases the variants remained of unknown significance. In one of the 32 cases dystrophinopathy could be excluded. In the remaining 10 cases, the variant was likely benign. Our results show the importance of additional genetic analyses and clinical follow up after potentially incidental findings of copy number variants in the DMD gene. Moreover, our study provides insight in the possible effect of intragenic copy number variants in the DMD gene. Therefore, the article can provide guidance in the interpretation of copy number variants in the DMD gene, for example once DMD is included in newborn screening.Show less

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Significance of incidental copy number variants in the Duchenne muscular dystrophy gene