Molecular Analysis-Based Genetic Characterization of a Cohort of Patients with Duchenne and Becker Muscular Dystrophy in Eastern China  

作　　者：Hui-Hui Zhao Xue-Ping Sun Ming-Chao Shi Yong-Xiang Yi Hong Cheng Xing-Xia Wang Qing-Cheng Xu Hong-Ming Ma Hao-Quan Wu Qing-Wen Jin Qi Niu 

机构地区：[1]Oepartment of Neurology, The First Affiliated Hospital of Naniing Medical University, Nanjing, Jiangeu 210029, China [2]Department of Gynecology and Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China [3]Department of Neurology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu 211166, China [4]Department of Neurology, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, China [5]Department of Neurology, Nanjing First Hospital, Nanjing, Jiangsu 210012, China [6]Department of Biomedical Sciences, Texas Tech University Health Science Center, Texas 79430, USA

出　　处：《Chinese Medical Journal》2018年第7期770-775,共6页中华医学杂志（英文版）

基　　金：This study was supported by grants from the National Natural Science Foundation of China （No. 81671117）, the Jiangsu Province Natural Science Foundation （No. BK20141439）, and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions （No. JXC 10231802）.

摘　　要：Background： Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are common X-linked recessive neuromuscular disorders caused by mutations in dystrophin gene. Multiplex polymerase chain reaction （multiplex PCR） and multiplex ligation-dependent probe amplification （MLPA） are the most common methods for detecting dystrophin gene mutations, This study aimed to contrast the two methods and discern the genetic characterization of patients with DMD/BMD in Eastern China. Methods： We collected 121 probands, 64 mothers ofprobands, and 15 fetuses in our study. The dystrophin gene was detected by multiplex PCR primarily in 28 probands, and MLPA was used in multiplex PCR-negative cases subsequently. The dystrophin gene of the remaining 93 probands and 62 female potential carriers was tested by MLPA directly. In fetuses, multiplex PCR and MLPA were performed on 4 fetuses and 10 fetuses, respectively. In addition, sequencing was also performed in 4 probands with negative MLPA. Results： We found that 61.98% of the subjects had genetic mutations including deletions （50.41%） and duplications （11.57%）. There were 43.75% of mothers as carriers of the mutation. In 15 fetuses, 2 out of 7 male fetuses were found to be unhealthy and 2 out of 8 female fetuses were found to be carriers. Exons 3-26 and 45-52 have the maximum frequency in mutation regions. In the frequency ofexons individually, exon 47 and exon 50 were the most common in deleted regions and exons 5, 6, and 7 were found most frequently in duplicated regions. Conclusions： MLPA has better productivity and sensitivity than multiplex PCR. Prenatal diagnosis should be applied in DM D high-risk fetuses to reduce the disease incidence. Furthermore, it is the responsibility of physicians to inform female carriers the importance of prenatal diagnosis.Background： Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are common X-linked recessive neuromuscular disorders caused by mutations in dystrophin gene. Multiplex polymerase chain reaction （multiplex PCR） and multiplex ligation-dependent probe amplification （MLPA） are the most common methods for detecting dystrophin gene mutations, This study aimed to contrast the two methods and discern the genetic characterization of patients with DMD/BMD in Eastern China. Methods： We collected 121 probands, 64 mothers ofprobands, and 15 fetuses in our study. The dystrophin gene was detected by multiplex PCR primarily in 28 probands, and MLPA was used in multiplex PCR-negative cases subsequently. The dystrophin gene of the remaining 93 probands and 62 female potential carriers was tested by MLPA directly. In fetuses, multiplex PCR and MLPA were performed on 4 fetuses and 10 fetuses, respectively. In addition, sequencing was also performed in 4 probands with negative MLPA. Results： We found that 61.98% of the subjects had genetic mutations including deletions （50.41%） and duplications （11.57%）. There were 43.75% of mothers as carriers of the mutation. In 15 fetuses, 2 out of 7 male fetuses were found to be unhealthy and 2 out of 8 female fetuses were found to be carriers. Exons 3-26 and 45-52 have the maximum frequency in mutation regions. In the frequency ofexons individually, exon 47 and exon 50 were the most common in deleted regions and exons 5, 6, and 7 were found most frequently in duplicated regions. Conclusions： MLPA has better productivity and sensitivity than multiplex PCR. Prenatal diagnosis should be applied in DM D high-risk fetuses to reduce the disease incidence. Furthermore, it is the responsibility of physicians to inform female carriers the importance of prenatal diagnosis.

关 键 词：Becker Muscular Dystrophy Duchenne Muscular Dystrophy DYSTROPHIN Multiplex Ligation-dependent Probe Amplification Multiplex Polymerase Chain Reaction Prenatal Diagnosis 

分 类 号：Q78[生物学—分子生物学] S436.3[农业科学—农业昆虫与害虫防治]