title: Screening of Duchenne muscular dystrophy (DMD) mutations and investigating its mutational mechanism in Chinese patients.
abstract: Duchenne muscular dystrophy (DMD) is a common X-linked recessive disease of muscle degeneration and death. In order to provide accurate and reliable genetic counseling and prenatal diagnosis, we screened DMD mutations in a cohort of 119 Chinese patients using multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) followed by Sanger sequencing. In these unrelated DMD patients, we identified 11 patients with DMD small mutations (9.2%) and 81 patients with DMD deletions/duplications (del/dup) (68.1%), of which 64 (79.0%) were deletions, 16 (19.8%) were duplications, and one (1.2%) was both deletion and duplication. Furthermore, we analyzed the frequency of DMD breakpoint in the 64 deletion cases by calculating exon-deletion events of certain exon interval that revealed a novel mutation hotspot boundary. To explore why DMD rearrangement breakpoints were predisposed to specific regions (hotspot), we precisely characterized junction sequences of breakpoints at the nucleotide level in 21 patients with exon deleted/duplicated in DMD with a high-resolution SNP microarray assay. There were no exactly recurrent breakpoints and there was also no significant difference between single-exon del/dup and multiple-exon del/dup cases. The data from the current study provided a comprehensive strategy to detect DMD mutations for clinical practice, and identified two deletion hotspots at exon 43-55 and exon 10-23 by calculating exon-deletion events of certain exon interval. Furthermore, this is the first study to characterize DMD breakpoint at the nucleotide level in a Chinese population. Our observations provide better understanding of the mechanism for DMD gene rearrangements.
authors.affiliation: The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Developing Pediatrics, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Xuesha
authors.initials: X
authors.lastname: Xing
authors.affiliation: The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Wang
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Luo
mesh_terms: D002681:China; D002851:Chromatography, High Pressure Liquid; D043283:Chromosome Fragile Sites; D016189:Dystrophin / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D011296:Prenatal Diagnosis
chemical_list: C484258:DMD protein, human; D016189:Dystrophin