Tandem duplications of two separate fragments of the dystrophin gene in a patient with Duchenne muscular dystrophy.
Mutations in the dystrophin gene result in the most common inherited muscle disease, Duchenne muscular dystrophy (DMD). Duplications spanning one or more exons have been found to be the second most common disease-causing mutation in the dystrophin gene. Although the duplicated exons are commonly thought to be arranged in tandem, rare noncontiguous exon duplications have been disclosed without clarifying their location or orientation. Here we present the first report that details the exact locations and orientations of noncontiguous duplications in the dystrophin gene. Multiplex ligation-dependent probe amplification analysis of the dystrophin gene of a Japanese boy with DMD revealed that his genomic DNA contained duplications of exons from two separate fragments of the gene: one from exon 45 to exon 48 and the other from exon 55 to exon 63. To clarify the locations and orientations of the duplicated exons, reverse transcription-nested PCR analysis of dystrophin mRNA was conducted. Interestingly, the extra copies of exons 45-48 and exons 55-63 were found to be properly oriented between exons 48 and 49 and exons 63 and 64, respectively. These results indicated that two tandem duplication events occurred in the dystrophin gene of this patient and should contribute to the understanding of the duplication mechanisms that contribute to the development of DMD.
Zhang
Zhujun
Z
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan.
Takeshima
Yasuhiro
Y
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan.
Awano
Hiroyuki
H
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan.
Nishiyama
Atsushi
A
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan.
Okizuka
Yo
Y
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan.
Yagi
Mariko
M
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan.
Matsuo
Masafumi
M
Department of Pediatrics, Graduate School of Medicine Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, 650-0017, Japan. matsuo@kobe-u.ac.jp.
D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D017931:DNA Primers; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D005784:Gene Amplification; D020440:Gene Duplication; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D016189:Dystrophin; D012333:RNA, Messenger