Genetic analysis of 1051 Chinese families with Duchenne/Becker Muscular Dystrophy

Autor: Li'na Liu, Siying Cui, Yuxia Yang, Xingjian Zhong, Xiangdong Kong, Lingrong Kong
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Proband
musculoskeletal diseases
congenital
hereditary
and neonatal diseases and abnormalities
Sanger sequencing
lcsh:Internal medicine
lcsh:QH426-470
Duchenne muscular dystrophy
Prenatal diagnosis
Multiplex ligation-dependent probe amplification (MLPA)
030105 genetics & heredity
Gene mutation
Genetic analysis
03 medical and health sciences
symbols.namesake
Asian People
Genetics
Humans
Medicine
Genetic Testing
Multiplex ligation-dependent probe amplification
Muscular dystrophy
lcsh:RC31-1245
Genetic Association Studies
Genetics (clinical)
business.industry
Next-generation sequencing (NGS)
High-Throughput Nucleotide Sequencing
Exons
medicine.disease
Muscular Dystrophy
Duchenne
lcsh:Genetics
030104 developmental biology
Child
Preschool
Mutation
Duchenne muscular dystrophy (DMD)
Gene mutations
symbols
Female
business
Multiplex Polymerase Chain Reaction
Research Article
Zdroj: BMC Medical Genetics, Vol 20, Iss 1, Pp 1-6 (2019)
BMC Medical Genetics
ISSN: 1471-2350
DOI: 10.1186/s12881-019-0873-0
Popis: Background Duchenne Muscular Dystrophy (DMD) is the most common muscle disease in children, and there are no effective therapies for DMD or Becker Muscular Dystrophy (BMD). Currently, targeted gene therapy treatments have emerged. As a result, genetic diagnosis is the basis of treatment. In addition, genetic and prenatal diagnosis significantly reduces their incidence rates. This study combines the application of multiplex ligation-dependent probe amplification technology (MLPA) and “next-generation” sequencing technology (NGS) as the most economical and efficient method of diagnosis. Therefore, in the diagnosis of DMD/BMD, patients’ MLPA data are first used to detect DMD gene deletions or duplications, and NGS and Sanger sequencing are then applied to exclude MLPA-negative samples. Meanwhile, polymerase chain reaction (PCR) is used to detect single exon deletions to exclude false-positives in MLPA caused by point mutations. Methods In this study, we recruited 1051 proband families of DMD from 2016 to 2018 and had access to information that could identify individual participants during or after data collection. Patients who were diagnosed with DMD were first tested by MLPA. MLPA results with single exon deletions were validated with PCR amplification and Sanger sequencing. The negative results of MLPA were further analysed with NGS and validated by Sanger sequencing. For novel missense mutations, phenotype-genotype correlations were analysed using PolyPhen2 and mutation taster. All methods were performed in accordance with the relevant guidelines and regulations. Results DMD mutations were identified in 1029 families (97.91%, 1029/1051). Large deletions, duplications, and small mutations accounted for 70.41% (740/1051), 8.28% (87/1051), and 19.12% (201/1051) of all cases, respectively. There were 205 small mutation types, 53 of which were novel. The rate of de novo mutations was 39.45% (187/474) and was higher in large duplications (49.53%, 157/317). Among 68 asymptomatic patients (
Databáze: OpenAIRE
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