[1]杨　乐,赵斯钰,郑妍妍,等.中国西北地区102例儿童Duchenne型肌营养不良基因突变及家系分析研究[J].现代检验医学杂志,2021,36(05):12-15.[doi:10.3969/j.issn.1671-7414.2021.05.003]
　YANG Le,ZHAO Si-yu,ZHENG Yan-yan,et al.102 Cases of Duchenne Muscular Dystrophy in Children in NorthwestChina Study on Gene Mutation and Family Analysis[J].Journal of Modern Laboratory Medicine,2021,36(05):12-15.[doi:10.3969/j.issn.1671-7414.2021.05.003]
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中国西北地区102例儿童Duchenne型肌营养不良基因突变及家系分析研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第36卷
期数:
2021年05期
页码:
12-15
栏目:
论　著
出版日期:
2021-10-14

文章信息/Info

Title:
102 Cases of Duchenne Muscular Dystrophy in Children in NorthwestChina Study on Gene Mutation and Family Analysis
文章编号:
1671-7414（2021）05-012-05
作者:
杨　乐; 赵斯钰; 郑妍妍; 等
（西安市儿童医院神经内科，西安 710002）
Author(s):
YANG Le; ZHAO Si-yu; ZHENG Yan-yan; LI Tao-li; SONG Xi-xiao; WANG Yan
（Department of Neurology, Xi’an Children’s Hospital，Xi’an 710002, China）
关键词:
Duchenne型肌营养不良; 基因; 突变; 家系
分类号:
R746.2；Q754
DOI:
10.3969/j.issn.1671-7414.2021.05.003
文献标志码:
A
摘要:
目的　了解西北地区Duchenne型肌营养不良症(DMD)患者基因突变特点。方法　收集2014年7月～2020年6月的102例DMD患者作为研究对象，采用多重连接依赖探针扩增（multiplex ligationdependent probe amplification, MLPA）技术、二代基因测序（next-generation sepuencing, NGS)技术及Sanger测序方法进行基因检测，分析西北地区DMD患者基因缺失突变、重复突变、点突变的分布区域特点，且对2个DMD家系基因特点进行分析。结果　102例DMD患者，72.5%来源于遗传，27.5%为新发突变。基因突变类型中，85.3%为片段缺失，6.9%为片段重复，7.8%为点突变。片段缺失突变中，≤5个数目的外显子缺失最为常见，占比为66.6%；外显子44~54是最常见的缺失区域，外显子2是最常见的重复区域。2个家系研究，家系1中突变位点为缺失突变的热点区域，外显子45~51区域；家系2中主要是重复突变，集中在外显子2和17~18区域。结论　大样本对西北地区DMD患者及家系的基因分析，可以进一步了解DMD患者基因谱，为基因治疗建立基础。
Abstract:
Objective　To investigate the genotype characteristics of Duchenne muscular dystrophy (DMD) in Northwest China.Methods　A total of 102 patients with DMD from July 2014 to June 2020 were collected as the research subjects. MLPA, NGSand Sanger sequencing were used for gene detection to analyze the regional characteristics of gene detection mutation, repeatedmutation and point mutation in DMD patients in Northwest China, and the genetic characteristics of two DMD families wereanalyzed. Results　Of the 102 patients with DMD，72.5% were genetic and 27.5% were new mutations. Among the mutanttypes, 85.3% were fragment deletion, 6.9% were fragment duplication and 7.8% were point mutations. Among the fragmentdeletion mutations, the deletion of exon with ≤ 5 numbers was the most common, accounting for 66.6%. Exon 44~54 was themost common missing region, and exon 2 was the most common repeating region. Two families were studied. In family 1, themutation site was the hot spot of deletion mutation, in the exon 45~51 region. Family 2 was dominated by repeated mutations,concentrated in exon 2 and the 17~18 region. Conclusion　Genetic analysis of large samples of DMD patients and their familiesin Northwest China could further understand the gene profile of DMD patients, and lay a foundation for gene therapy.

参考文献/References:

[1] KE Qing, ZHAO Zhengyan, GRIGGS R, et al.Newborn screening for Duchenne muscular dystrophyin China: follow-up diagnosis and subsequenttreatment[J]. World Journal of Pediatrics, 2017, 13(3):197-201.
[2] 张瑶, 汤颖, 张成.Duchenne 型肌营养不良心脏损害研究进展[J].中国现代神经疾病杂志,2013,13(5):453-456.ZHANG Yao, TANG Ying, ZHANG Cheng. Progressstudy of the cardiac damage in Duchenne musculardystrophy [J]. Chinese Journal of ContemporaryNeurology and Neurosurgery, 2013,13(5):453-456.
[3] LAING N G, DAVIS M R, BAYLEY K, et al.Molecular diagnosis of duchenne muscular dystrophy:past, present and future in relation to implementingtherapies[J]. The Clinical Biochemist. Reviews /Australian Association of Clinical Biochemists, 2011,32(3): 129-134.
[4] ABBS S, TUFFERY-GIRAUD S, BAKKER E, etal. Best practice guidelines on molecular diagnosticsin Duchenne/Becker muscular dystrophies[J].Neuromuscular Disorders, 2010, 20(6): 422-427.
[5] 王皖骏，朱海燕，朱瑞芳，等．假肥大型肌营养不良症家系的基因检测与产前诊断[J]. 中华医学遗传学杂志,2013,30(1):45~48.WANG Wanjun, ZHU Haiyan, ZHU Ruifang, et al.Mutation analysis and prenatal diagnosis of familiesaffected with Duchenne and Becker muscular dystrophy[J]. Chinese Journal of Medical Genetics，2013,30(1):45-48.
[6] 何展文, 陈启慧, 李平甘, 等. 多重连接探针扩增和二代测序技术检测Duchenne 型肌营养不良基因分析[J]. 中国实用神经疾病杂志,2020,23(14):1209-1212.HE Zhanwen, CHEN Qihui, LI Pinggan, et al. Geneticsanalysis of patients with Duchenne muscular dystrophyusing multiplex ligation-dependent probe ampli-ficationand next-generation sequencing [J]. Chinese Journal ofPractical Nervous Diseases, 2020,23(14):1209-1212.
[7] 李双, 白莹, 赵振华, 等.81 例假肥大型肌营养不良症患者基因突变分析[J]. 中华医学遗传学杂志,2016, 33(6):762-776．LI Shuang, BAI Ying, ZHAO Zhenhua, et al. Mutationanalysis of 81 cases with Duchenne/Becker musculardystrophy [J]. Chinese Journal of Medical Genetics,2016, 33( 6):762-776．
[8] NARDES F, ARAUJO A P, RIBEIRO M G. Mentalretardation in Duchenne muscular dystrophy[J]. Journalde Pediatria, 2012, 88(1): 6-16.
[9] BEYT?A M L, VRY J, KIRSCHNER J. Drug treatmentof Duchenne muscular dystrophy: available evidenceand perspectives[J]. Acta Myologica, 2012, 31(1): 4-8.
[10] KOENIG M, HOFFMAN E P, BERTELSON C J,et al. Complete cloning of the Duehenne musculardystrophy(DMD)cDNA and preliminarygenomicorganization of the DMD gene in normal and affectedindividuals[J]. Cell, 1987,50(3):509-517.
[11] 韩春锡，林婧娴，吴维青，等. 婴幼儿杜氏型肌营养不良临床表现及其基因和骨骼肌病理特征[J]. 中国循证儿科杂志, 2013, 8(4):290-294.HAN Chunxi，LIN Jingxian，WU Weiqing, et al.Clinical,genetic and pathologic features of infantDuchenne muscular dystrophy [J]. Chinese Journal ofEvidence Based Pediatrics, 2013, 8(4): 290-294.
[12] WEIN N, ALFANO L, FLANIGAN K M. Geneticsand emerging treatments for Duchenne and Beckermuscular dystrophy[J]. Pediatric Clinics of NorthAmerica, 2015, 62(3): 723-742.
[13] SARDONE V, ZHOU Haiyan, MUNTONI F,et al. Antisense oligonucleotide-based therapyfor neuromuscular disease[J]. Molecules (Basel,Switzerland), 2017, 22(4): 563.
[14] MAGRI F, DEL BO R, D’ANGELO M G, et al. Clinicaland molecular characterization of a cohort of patientswith novel nucleotide alterations of the Dystrophingene detected by direct sequencing[J]. BMC MedicalGenetics, 2011, 12(1) :37.
[15] YANG Juan, LI Shaoyin, LI Yaqin, et al. MLPA-basedgenotype-phenotype analysis in 1 053 Chinese patientswith DMD/BMD[J]. BMC Medical Genetics, 2013,14(1): 29.
[16] TAKESHIMA Y, YAGI M, OKIZUKA Y, et al.Mutation spectrum of the dystrophin gene in 442Duchenne/Becker muscular dystrophy cases from oneJapanese referral center[J]. Journal of Human Genetics,2010, 55(6): 379-388.
[17] MA Peipei, ZHANG Shu, ZHANG Hao, etal. Comprehensive genetic characteristics ofdystrophinopathies in China[J]. Orphanet Journal ofRare Diseases, 2018, 13(1): 109.
[18] 钟京梓．肌营养不良基因诊断及新突变致病性研究[D]. 南宁: 广西医科大学,2018.ZHONG Jingzi. Study on gene diagnosis andnew pathogenicity of muscular dystrophy [D].Nanning:Guangxi Medical University, 2018.
[19] 陆盈, 孙顺昌．MLPA 技术对Duchenne 肌营养不良症患者基因外显子缺失和重复的诊断价值[J]. 现代检验医学杂志, 2017,32(4):12-15.LU Ying, SUN Shunchang. Deletion and duplicationin the DMD gene detected by MLPA[J]. Journal ofModern Laboratory Medicine， 2017,32(4):12-15.
[20] 洪莎, 赵冬莹, 谢利娟, 等.2 个中国汉族假肥大型进行性肌营养不良家系分析[J]. 上海交通大学学报( 医学版),2018,38(10):1223-1228.HONG Sha, ZHAO Dongying, XIE Lijuan，et al.Analysis of two Chinese Han families with Duchenne/Becker muscular dystrophy[J]. Journal of ShanghaiJiaotong University(Medical Science), 2018, 38 (10):1223-1228.
[21] BIRNKRANT D J, BUSHBY K, CARLA M B, et al.Diagnosis and management of Duchenne musculardystrophy, part 1: diagnosis, and neuromuscular,rehabilitation, endocrine, and gastrointestinal andnutritional management[J]. The Lancet Neurology,2018, 17(3): 251-267.

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备注/Memo

备注/Memo:
基金项目：陕西省社会发展科技攻关项目，编号2015SF214。
作者简介：杨乐（1987-），女，硕士，主治医师，专业：儿童神经系统疾病，E-mail:yler-428@126.com。
通讯作者：王燕（1980-），女，在读博士，副主任医师，专业：儿童神经系统疾病，E-mail:wy800709@163.com。
更新日期/Last Update: 1900-01-01