Details

Autor(en) / Beteiligte

• White, S.J.
• Aartsma-Rus, A.
• Flanigan, K.M.
• Weiss, R.B.
• Kneppers, A.L.J.
• Lalic, T.
• Janson, A.A.M.
• Ginjaar, H.B.
• Breuning, M.H.
• den Dunnen, J.T.

Titel

Duplications in the DMD gene

Ist Teil von

• Human mutation, 2006-09, Vol.27 (9), p.938-945

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2006

Quelle

Access via Wiley Online Library

Beschreibungen/Notizen

• The detection of duplications in Duchenne (DMD)/Becker Muscular Dystrophy (BMD) has long been a neglected issue. However, recent technological advancements have significantly simplified screening for such rearrangements. We report here the detection and analysis of 118 duplications in the DMD gene of DMD/BMD patients. In an unselected patient series the duplication frequency was 7%. In patients already screened for deletions and point mutations, duplications were detected in 87% of cases. There were four complex, noncontiguous rearrangements, with two also involving a partial triplication. In one of the few cases where RNA was analyzed, a seemingly contiguous duplication turned out to be a duplication/deletion case generating a transcript with an unexpected single‐exon deletion and an initially undetected duplication. These findings indicate that for clinical diagnosis, duplications should be treated with special care, and without further analysis the reading frame rule should not be applied. As with deletions, duplications occur nonrandomly but with a dramatically different distribution. Duplication frequency is highest near the 5′ end of the gene, with a duplication of exon 2 being the single most common duplication identified. Analysis of the extent of 11 exon 2 duplications revealed two intron 2 recombination hotspots. Sequencing four of the breakpoints showed that they did not arise from unequal sister chromatid exchange, but more likely from synthesis‐dependent nonhomologous end joining. There appear to be fundamental differences therefore in the origin of deletions and duplications in the DMD gene. Hum Mutat 27(9), 938–945, 2006. Published 2006 Wiley‐Liss, Inc.